Autophagy - Revision history

Dmitry Dzhagarov: /* Mitophagy */

2023-11-05T10:30:43Z

Mitophagy

← Older revision		Revision as of 10:30, 5 November 2023
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	The selective degradation of [[mitochondria]] through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref>		The selective degradation of [[mitochondria]] through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref>

	Mitophagy declines with age, which leads to the accumulation of damaged mitochondria and the development of a number of age-associated diseases, including Alzheimer's and Parkinson's. Some mitophagy-inducing substances (e.g. resveratrol, metformin and urolithin A) simultaneously activate the biogenesis of new mitochondria, thus promoting health despite aging.<ref>Srivastava, V., & Gross, E. (2023). Mitophagy-promoting agents and their ability to promote healthy-aging. Biochemical Society Transactions, BST20221363. PMID: 37650304 [https://doi.org/10.1042/BST20221363 DOI: 10.1042/BST20221363]</ref>		Mitophagy declines with age, which leads to the accumulation of damaged mitochondria and the development of a number of age-associated diseases, including Alzheimer's and Parkinson's. Some mitophagy-inducing substances (e.g. resveratrol, metformin and urolithin A) simultaneously activate the biogenesis of new mitochondria, thus promoting health despite aging.<ref>Srivastava, V., & Gross, E. (2023). Mitophagy-promoting agents and their ability to promote healthy-aging. Biochemical Society Transactions, BST20221363. PMID: 37650304 [https://doi.org/10.1042/BST20221363 DOI: 10.1042/BST20221363]</ref><ref>Dong, Y., Zhuang, X. X., Wang, Y. T., Tan, J., Feng, D., Li, M., ... & Lu, J. H. (2023). Chemical mitophagy modulators: drug development strategies and novel regulatory mechanisms. Pharmacological Research, 106835. PMID: 37348691 [https://doi.org/10.1016/j.phrs.2023.106835 DOI: 10.1016/j.phrs.2023.106835]</ref>

	=== Autophagy and longevity ===		=== Autophagy and longevity ===

Dmitry Dzhagarov: /* Mitophagy */

2023-11-05T09:28:48Z

Mitophagy

← Older revision		Revision as of 09:28, 5 November 2023
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	===== Mitophagy =====		===== Mitophagy =====
			The selective degradation of [[mitochondria]] through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref>

	~~The selective degradation~~ of [[mitochondria~~]] through autophagy is known as mitophagy~~. ~~There are multiple sub-types of~~ mitophagy~~, such as PINK1/Parkin~~-~~dependant~~, ~~Ubiquitin-independent receptor-mediated~~ and ~~others like piecemeal mitophagy~~.<ref>~~Bakula D~~, ~~Scheibye-Knudsen M~~. ~~MitophAging:~~ Mitophagy ~~in Aging~~ and ~~Disease~~. ~~Front Cell Dev Biol~~. ~~2020 Apr 15;8~~:~~239~~. ~~doi:~~ 10.~~3389~~/~~fcell.2020.00239. PMID~~: ~~32373609; PMCID: PMC7179682~~.</ref>		Mitophagy declines with age, which leads to the accumulation of damaged mitochondria and the development of a number of age-associated diseases, including Alzheimer's and Parkinson's. Some mitophagy-inducing substances (e.g. resveratrol, metformin and urolithin A) simultaneously activate the biogenesis of new mitochondria, thus promoting health despite aging.<ref>Srivastava, V., & Gross, E. (2023). Mitophagy-promoting agents and their ability to promote healthy-aging. Biochemical Society Transactions, BST20221363. PMID: 37650304 [https://doi.org/10.1042/BST20221363 DOI: 10.1042/BST20221363]</ref>

	=== Autophagy and longevity ===		=== Autophagy and longevity ===

Andrea: category change

2022-12-27T12:49:30Z

category change

← Older revision		Revision as of 12:49, 27 December 2022
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	<references />		<references />
	~~[[Category:Longevity pathways]]~~
	[[Category:Main list]]		[[Category:Main list]]
			[[Category:Aging pathways and hallmarks]]

Andrea at 11:15, 27 December 2022

2022-12-27T11:15:03Z

← Older revision		Revision as of 11:15, 27 December 2022
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	<references />		<references />
	[[Category:Longevity pathways]]		[[Category:Longevity pathways]]
			[[Category:Main list]]

Andrea: category change

2022-12-27T09:38:41Z

category change

← Older revision		Revision as of 09:38, 27 December 2022
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	<references />		<references />
	[[Category:Longevity]]		[[Category:Longevity pathways]]

Andrea: added interlink

2022-11-15T13:12:11Z

added interlink

← Older revision		Revision as of 13:12, 15 November 2022
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	=== Autophagy and longevity ===		=== Autophagy and longevity ===
	The connections between dysfunctional autophagy with aging and age-related diseases are abundant, and compromised autophagy is considered to be a hallmark of aging.<ref name=":0" /><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref> Up-regulating autophagy via genetic or pharmacological tools has shown to promote longevity in nematodes, fruit flies and mice.<ref>Simonsen, A. et al. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult ''Drosophila''. ''Autophagy'' 4, 176–184 (2008).</ref><ref>Pyo, J. O. et al. Overexpression of Atg5 in mice activates autophagy and extends lifespan. ''Nat. Commun.'' 4, 2300 (2013).</ref><ref>Fernandez, A. F. et al. Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice. ''Nature'' 558, 136–140 (2018).</ref><ref>Ulgherait, M., Rana, A., Rera, M., Graniel, J. & Walker, D. W. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. ''Cell Rep.'' 8, 1767–1780 (2014).</ref><ref>Lapierre, L. R. et al. The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in ''Caenorhabditiselegans''. ''Nat. Commun.'' 4, 2267 (2013).</ref> On the other hand, in line with these findings, inhibiting selective or non-selective autophagy leads to accelerated aging and functional tissue decline.<ref name=":0" />		The connections between dysfunctional autophagy with aging and age-related diseases are abundant, and compromised autophagy is considered to be a [[Hallmarks of aging\|hallmark of aging]].<ref name=":0" /><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref> Up-regulating autophagy via genetic or pharmacological tools has shown to promote longevity in nematodes, fruit flies and mice.<ref>Simonsen, A. et al. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult ''Drosophila''. ''Autophagy'' 4, 176–184 (2008).</ref><ref>Pyo, J. O. et al. Overexpression of Atg5 in mice activates autophagy and extends lifespan. ''Nat. Commun.'' 4, 2300 (2013).</ref><ref>Fernandez, A. F. et al. Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice. ''Nature'' 558, 136–140 (2018).</ref><ref>Ulgherait, M., Rana, A., Rera, M., Graniel, J. & Walker, D. W. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. ''Cell Rep.'' 8, 1767–1780 (2014).</ref><ref>Lapierre, L. R. et al. The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in ''Caenorhabditiselegans''. ''Nat. Commun.'' 4, 2267 (2013).</ref> On the other hand, in line with these findings, inhibiting selective or non-selective autophagy leads to accelerated aging and functional tissue decline.<ref name=":0" />

	Many longevity pathways converge on autophagy genes and can regulate lifespan in animal models such as fruit flies or worms.<ref name=":4">Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants.<ref name=":4" /><ref>Mörck, C., Pilon, M. ''C. elegans''feeding defective mutants have shorter body lengths and increased autophagy. ''BMC Dev Biol'' 6, 39 (2006). <nowiki>https://doi.org/10.1186/1471-213X-6-39</nowiki></ref> Furthermore, the 60% lifespan extension of daf-2 loss-of-function mutants is dependent on autophagic genes such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref>		Many longevity pathways converge on autophagy genes and can regulate lifespan in animal models such as fruit flies or worms.<ref name=":4">Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants.<ref name=":4" /><ref>Mörck, C., Pilon, M. ''C. elegans''feeding defective mutants have shorter body lengths and increased autophagy. ''BMC Dev Biol'' 6, 39 (2006). <nowiki>https://doi.org/10.1186/1471-213X-6-39</nowiki></ref> Furthermore, the 60% lifespan extension of daf-2 loss-of-function mutants is dependent on autophagic genes such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref>

Andrea: /* Chaperone-assisted selective autophagy (CASA) */

2022-11-15T12:54:53Z

Chaperone-assisted selective autophagy (CASA)

← Older revision		Revision as of 12:54, 15 November 2022
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	~~{{Draft-article}}~~		Autophagy (“''auto''” meaning “self”, and “''phagy''” meaning “to eat”) is a catabolic process highly conserved in eukaryotes, in which cytoplasmic components are delivered to the lysosome and degraded. It is a key process for the regulation of cellular energetic equilibrium and plays a housekeeping role by removing cellular waste, damaged organelles, aggregated or misfolded proteins and even intracellular pathogens.<ref name=":0">Aman, Y., Schmauck-Medina, T., Hansen, M. ''et al.'' Autophagy in healthy aging and disease. ''Nat Aging''1, 634–650 (2021). <nowiki>https://doi.org/10.1038/s43587-021-00098-4</nowiki></ref><ref>Glick, D., Barth, S., & Macleod, K. (2010). Autophagy: cellular and molecular mechanisms. ''The Journal Of Pathology'', ''221''(1), 3-12. doi: 10.1002/path.2697</ref> The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.<ref>Maria Fimia, G., Stoykova, A., Romagnoli, A., Giunta, L., Di Bartolomeo, S., & Nardacci, R. et al. (2007). Ambra1 regulates autophagy and development of the nervous system. ''Nature'', ''447''(7148), 1121-1125. doi: 10.1038/nature05925</ref><ref>Qu, X., Zou, Z., Sun, Q., Luby-Phelps, K., Cheng, P., & Hogan, R. et al. (2007). Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. ''Cell'', ''128''(5), 931-946. doi: 10.1016/j.cell.2006.12.044</ref> Autophagy promotes cell survival, facilitates bioenergetic homeostasis and can promote cell death.<ref>Das, G., Shravage, B.V. and Baehrecke, E.H. (2012) “Regulation and function of autophagy during cell survival and cell death,” ''Cold Spring Harbor Perspectives in Biology'', 4(6). <nowiki>https://doi.org/10.1101/cshperspect.a008813</nowiki>. </ref>

	Autophagy (“''auto''” meaning “self”, and “''phagy''” meaning “to eat”) is a catabolic process highly conserved in eukaryotes, in which cytoplasmic components are delivered to the lysosome and degraded. It is a key process for the regulation of cellular energetic equilibrium and plays a housekeeping role by removing cellular waste, damaged organelles, aggregated or misfolded proteins and even intracellular pathogens.<ref name=":0">Aman Y, Schmauck-Medina T, Hansen M~~, Morimoto RI, Simon AK, Bjedov I, Palikaras K, Simonsen A, Johansen T, Tavernarakis N, Rubinsztein DC, Partridge L, Kroemer G, Labbadia J, Fang EF~~. Autophagy in healthy aging and disease. Nat Aging~~. 2021 Aug;~~1(8):~~634-650~~. ~~doi:~~ 10.1038/s43587-021-00098-4~~. Epub 2021 Aug 12. PMID: 34901876; PMCID: PMC8659158.~~</ref><ref>Glick, D., Barth, S., & Macleod, K. (2010). Autophagy: cellular and molecular mechanisms. ''The Journal Of Pathology'', ''221''(1), 3-12. doi: 10.1002/path.2697</ref> The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.<ref>Maria Fimia, G., Stoykova, A., Romagnoli, A., Giunta, L., Di Bartolomeo, S., & Nardacci, R. et al. (2007). Ambra1 regulates autophagy and development of the nervous system. ''Nature'', ''447''(7148), 1121-1125. doi: 10.1038/nature05925</ref><ref>Qu, X., Zou, Z., Sun, Q., Luby-Phelps, K., Cheng, P., & Hogan, R. et al. (2007). Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. ''Cell'', ''128''(5), 931-946. doi: 10.1016/j.cell.2006.12.044</ref>

	=== Types of autophagy ===		=== Types of autophagy ===
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	==== Chaperone-assisted selective autophagy (CASA) ====		==== Chaperone-assisted selective autophagy (CASA) ====
			CASA is an autophagy process that selective degrades chaperone-bound proteins in lysosomes.<ref>Gamerdinger, M. ''et al.'' (2009) “Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3,” ''The EMBO Journal'', 28(7), pp. 889–901. Available at: <nowiki>https://doi.org/10.1038/emboj.2009.29</nowiki>. </ref> Degradation of primed ubiquitinated chaperones is essential for protein quality control. CASA is critical for muscle maintenance and it is induced in response to resistance exercise in human skeletal muscle.<ref>Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11(3):538-46. doi: 10.1080/15548627.2015.1017186. </ref> Pathogenic forms of the Huntingtin protein, which may lead to Huntington's disease, are degraded by chaperone-assisted selective autophagy.<ref>Carra S, Seguin SJ, Landry J (January 2008). "HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy". ''Autophagy''. '''4''' (2): 237–9. doi:10.4161/auto.5407</ref>

	==== Organelle-specific autophagy ====		==== Organelle-specific autophagy ====
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	=== Autophagy and longevity ===		=== Autophagy and longevity ===
	The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0" /> Autophagy ~~promotes~~ cell ~~survival~~, ~~facilitates bioenergetic homeostasis~~ and ~~can promote cell death~~.<ref>~~Das~~, G., ~~Shravage~~, B.V. and ~~Baehrecke, E~~.H. (~~2012~~) ~~“Regulation and function~~ of autophagy ~~during cell survival~~ and cell ~~death,”~~ ''~~Cold Spring Harbor Perspectives in Biology~~'', 4(6). <~~nowiki~~>~~https://doi~~.~~org/10~~.~~1101/cshperspect~~.~~a008813~~</~~nowiki~~>. </~~ref~~>		The connections between dysfunctional autophagy with aging and age-related diseases are abundant, and compromised autophagy is considered to be a hallmark of aging.<ref name=":0" /><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref> Up-regulating autophagy via genetic or pharmacological tools has shown to promote longevity in nematodes, fruit flies and mice.<ref>Simonsen, A. et al. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult ''Drosophila''. ''Autophagy'' 4, 176–184 (2008).</ref><ref>Pyo, J. O. et al. Overexpression of Atg5 in mice activates autophagy and extends lifespan. ''Nat. Commun.'' 4, 2300 (2013).</ref><ref>Fernandez, A. F. et al. Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice. ''Nature'' 558, 136–140 (2018).</ref><ref>Ulgherait, M., Rana, A., Rera, M., Graniel, J. & Walker, D. W. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. ''Cell Rep.'' 8, 1767–1780 (2014).</ref><ref>Lapierre, L. R. et al. The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in ''Caenorhabditiselegans''. ''Nat. Commun.'' 4, 2267 (2013).</ref> On the other hand, in line with these findings, inhibiting selective or non-selective autophagy leads to accelerated aging and functional tissue decline.<ref name=":0" />

	Many longevity pathways converge on autophagy genes and regulate lifespan in animal models such as fruit flies or worms.<ref name=":4">Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> Inhibiting selective or non-selective autophagy has demonstrated to lead to accelerated aging and functional tissue decline in a variety of organisms.<ref>Aman, Y., Schmauck-Medina, T., Hansen, M. ''et al.'' Autophagy in healthy aging and disease. ''Nat Aging''1, 634–650 (2021). <nowiki>https://doi.org/10.1038/s43587-021-00098-4</nowiki></ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants.<ref name=":4" /> Furthermore, the 60% lifespan extension of daf-2 loss-of-function mutants is dependent on autophagic genes such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref>		Many longevity pathways converge on autophagy genes and can regulate lifespan in animal models such as fruit flies or worms.<ref name=":4">Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants.<ref name=":4" /><ref>Mörck, C., Pilon, M. ''C. elegans''feeding defective mutants have shorter body lengths and increased autophagy. ''BMC Dev Biol'' 6, 39 (2006). <nowiki>https://doi.org/10.1186/1471-213X-6-39</nowiki></ref> Furthermore, the 60% lifespan extension of daf-2 loss-of-function mutants is dependent on autophagic genes such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref>

	<references />		<references />
	[[Category:Longevity]]		[[Category:Longevity]]

Andrea at 19:37, 14 November 2022

2022-11-14T19:37:57Z

← Older revision		Revision as of 19:37, 14 November 2022
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	The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0" /> Autophagy promotes cell survival, facilitates bioenergetic homeostasis and can promote cell death.<ref>Das, G., Shravage, B.V. and Baehrecke, E.H. (2012) “Regulation and function of autophagy during cell survival and cell death,” ''Cold Spring Harbor Perspectives in Biology'', 4(6). <nowiki>https://doi.org/10.1101/cshperspect.a008813</nowiki>. </ref>		The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0" /> Autophagy promotes cell survival, facilitates bioenergetic homeostasis and can promote cell death.<ref>Das, G., Shravage, B.V. and Baehrecke, E.H. (2012) “Regulation and function of autophagy during cell survival and cell death,” ''Cold Spring Harbor Perspectives in Biology'', 4(6). <nowiki>https://doi.org/10.1101/cshperspect.a008813</nowiki>. </ref>

	Many longevity pathways converge on autophagy genes and regulate lifespan in animal models such as fruit flies or worms.<ref>Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants. Furthermore, daf-2 loss-of-function ~~mutant 60% lifespan extension~~ is dependent on autophagic genes, such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref><references />		Many longevity pathways converge on autophagy genes and regulate lifespan in animal models such as fruit flies or worms.<ref name=":4">Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> Inhibiting selective or non-selective autophagy has demonstrated to lead to accelerated aging and functional tissue decline in a variety of organisms.<ref>Aman, Y., Schmauck-Medina, T., Hansen, M. ''et al.'' Autophagy in healthy aging and disease. ''Nat Aging''1, 634–650 (2021). <nowiki>https://doi.org/10.1038/s43587-021-00098-4</nowiki></ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants.<ref name=":4" /> Furthermore, the 60% lifespan extension of daf-2 loss-of-function mutants is dependent on autophagic genes such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref>

			<references />
	[[Category:Longevity]]		[[Category:Longevity]]

Andrea: Added figure and new sub-section

2022-11-14T19:11:19Z

Added figure and new sub-section

← Older revision		Revision as of 19:11, 14 November 2022
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	Autophagy (“''auto''” meaning “self”, and “''phagy''” meaning “to eat”) is a catabolic process highly conserved in eukaryotes, in which cytoplasmic components are delivered to the lysosome and degraded. It is a key process for the regulation of cellular energetic equilibrium and plays a housekeeping role by removing cellular waste, damaged organelles, aggregated or misfolded proteins and even intracellular pathogens.<ref name=":0" /><ref>Glick, D., Barth, S., & Macleod, K. (2010). Autophagy: cellular and molecular mechanisms. ''The Journal Of Pathology'', ''221''(1), 3-12. doi: 10.1002/path.2697</ref> The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.<ref>Maria Fimia, G., Stoykova, A., Romagnoli, A., Giunta, L., Di Bartolomeo, S., & Nardacci, R. et al. (2007). Ambra1 regulates autophagy and development of the nervous system. ''Nature'', ''447''(7148), 1121-1125. doi: 10.1038/nature05925</ref><ref>Qu, X., Zou, Z., Sun, Q., Luby-Phelps, K., Cheng, P., & Hogan, R. et al. (2007). Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. ''Cell'', ''128''(5), 931-946. doi: 10.1016/j.cell.2006.12.044</ref> The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0">Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, Bjedov I, Palikaras K, Simonsen A, Johansen T, Tavernarakis N, Rubinsztein DC, Partridge L, Kroemer G, Labbadia J, Fang EF. Autophagy in healthy aging and disease. Nat Aging. 2021 Aug;1(8):634-650. doi: 10.1038/s43587-021-00098-4. Epub 2021 Aug 12. PMID: 34901876; PMCID: PMC8659158.</ref>		Autophagy (“''auto''” meaning “self”, and “''phagy''” meaning “to eat”) is a catabolic process highly conserved in eukaryotes, in which cytoplasmic components are delivered to the lysosome and degraded. It is a key process for the regulation of cellular energetic equilibrium and plays a housekeeping role by removing cellular waste, damaged organelles, aggregated or misfolded proteins and even intracellular pathogens.<ref name=":0">Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, Bjedov I, Palikaras K, Simonsen A, Johansen T, Tavernarakis N, Rubinsztein DC, Partridge L, Kroemer G, Labbadia J, Fang EF. Autophagy in healthy aging and disease. Nat Aging. 2021 Aug;1(8):634-650. doi: 10.1038/s43587-021-00098-4. Epub 2021 Aug 12. PMID: 34901876; PMCID: PMC8659158.</ref><ref>Glick, D., Barth, S., & Macleod, K. (2010). Autophagy: cellular and molecular mechanisms. ''The Journal Of Pathology'', ''221''(1), 3-12. doi: 10.1002/path.2697</ref> The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.<ref>Maria Fimia, G., Stoykova, A., Romagnoli, A., Giunta, L., Di Bartolomeo, S., & Nardacci, R. et al. (2007). Ambra1 regulates autophagy and development of the nervous system. ''Nature'', ''447''(7148), 1121-1125. doi: 10.1038/nature05925</ref><ref>Qu, X., Zou, Z., Sun, Q., Luby-Phelps, K., Cheng, P., & Hogan, R. et al. (2007). Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. ''Cell'', ''128''(5), 931-946. doi: 10.1016/j.cell.2006.12.044</ref>

	=== Types of autophagy ===		=== Types of autophagy ===
			[[File:Types of autophagy.png\|thumb\|Main types of autophagy in mammals: Macroautophagy, chaperone-mediated autophagy and microautophagy.[https://www.cusabio.com/Cell-Biology/Autophagy.html]]]
	There are three well defined types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA)<ref>Parzych, K., & Klionsky, D. (2014). An Overview of Autophagy: Morphology, Mechanism, and Regulation. ''Antioxidants &Amp; Redox Signaling'', ''20''(3), 460-473. doi: 10.1089/ars.2013.5371</ref>, with chaperone-assisted selective autophagy (CASA) being recently added.<ref>Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11(3):538-46. doi: 10.1080/15548627.2015.1017186. PMID: 25714469; PMCID: PMC4502687.</ref><ref>Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010 Jan 26;20(2):143-8. doi: 10.1016/j.cub.2009.11.022. Epub 2010 Jan 7. PMID: 20060297.</ref> Despite differences in their mechanism of degradation and the molecular components they require, all three types of autophagy share in common the delivery of cytoplasmic cargo to the lysosome for proteolytic degradation. The different types of autophagy generally work in a coordinated manner to complement each other.<ref name=":1">Li, W.-wen, Li, J. and Bao, J.-ku (2011) “Microautophagy: Lesser-known self-eating,” ''Cellular and Molecular Life Sciences'', 69(7), pp. 1125–1136. Available at: <nowiki>https://doi.org/10.1007/s00018-011-0865-5</nowiki>.</ref>		There are three well defined types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA)<ref>Parzych, K., & Klionsky, D. (2014). An Overview of Autophagy: Morphology, Mechanism, and Regulation. ''Antioxidants &Amp; Redox Signaling'', ''20''(3), 460-473. doi: 10.1089/ars.2013.5371</ref>, with chaperone-assisted selective autophagy (CASA) being recently added.<ref>Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11(3):538-46. doi: 10.1080/15548627.2015.1017186. PMID: 25714469; PMCID: PMC4502687.</ref><ref>Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010 Jan 26;20(2):143-8. doi: 10.1016/j.cub.2009.11.022. Epub 2010 Jan 7. PMID: 20060297.</ref> Despite differences in their mechanism of degradation and the molecular components they require, all three types of autophagy share in common the delivery of cytoplasmic cargo to the lysosome for proteolytic degradation. The different types of autophagy generally work in a coordinated manner to complement each other.<ref name=":1">Li, W.-wen, Li, J. and Bao, J.-ku (2011) “Microautophagy: Lesser-known self-eating,” ''Cellular and Molecular Life Sciences'', 69(7), pp. 1125–1136. Available at: <nowiki>https://doi.org/10.1007/s00018-011-0865-5</nowiki>.</ref>

	==== Macroautophagy ====		==== Macroautophagy ====
	Due to its role in disease, macro-autophagy in particular has been the main focus of research over the past few decades, and often the term “autophagy” is used to refer to the macro-autophagy type of autophagy.<ref>Ichimiya, T. ''et al.'' (2020) “Autophagy and autophagy-related diseases: A Review,” ''International Journal of Molecular Sciences'', 21(23), p. 8974. Available at: <nowiki>https://doi.org/10.3390/ijms21238974</nowiki>.</ref>		Due to its role in disease, macro-autophagy in particular has been the main focus of research over the past few decades, and often the term “autophagy” is used to refer to the macro-autophagy type of autophagy.<ref>Ichimiya, T. ''et al.'' (2020) “Autophagy and autophagy-related diseases: A Review,” ''International Journal of Molecular Sciences'', 21(23), p. 8974. Available at: <nowiki>https://doi.org/10.3390/ijms21238974</nowiki>.</ref> Membrane structures in the cytoplasm form autophagosomes, a spherical structure with double-layer membranes

	==== Microautophagy ====		==== Microautophagy ====
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	===== Mitophagy =====		===== Mitophagy =====
	The selective degradation of [[mitochondria]] through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref><references />
			The selective degradation of [[mitochondria]] through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref>

			=== Autophagy and longevity ===
			The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0" /> Autophagy promotes cell survival, facilitates bioenergetic homeostasis and can promote cell death.<ref>Das, G., Shravage, B.V. and Baehrecke, E.H. (2012) “Regulation and function of autophagy during cell survival and cell death,” ''Cold Spring Harbor Perspectives in Biology'', 4(6). <nowiki>https://doi.org/10.1101/cshperspect.a008813</nowiki>. </ref>

			Many longevity pathways converge on autophagy genes and regulate lifespan in animal models such as fruit flies or worms.<ref>Tóth, M.L. ''et al.'' (2008) “Longevity pathways converge on autophagy genes to regulate life span in''caenorhabditis elegans'',” ''Autophagy'', 4(3), pp. 330–338. Available at: <nowiki>https://doi.org/10.4161/auto.5618</nowiki>. </ref> The process of autophagy is also up-regulated in long-lived ''C. elegans'' mutants such as the insulin/insulin-like growth factor (IGF)-1 receptor homolog [[FOXO longevity genes\|daf-2 mutant]] or feeding-defective mutants. Furthermore, daf-2 loss-of-function mutant 60% lifespan extension is dependent on autophagic genes, such as bec-1, lgg-1, atg-7 and atg-12.<ref>Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in ''C. elegans''. ''Science'' 301, 1387–1391 (2003).</ref><ref>Hansen, M., Rubinsztein, D. C. & Walker, D. W. Autophagy as a promoter of longevity: insights from model organisms. ''Nat. Rev. Mol. Cell Biol.'' 19, 579–593 (2018).</ref><ref>Leidal, A. M., Levine, B. & Debnath, J. Autophagy and the cell biology of age-related disease. ''Nat. Cell Biol.'' 20, 1338–1348 (2018).</ref><references />
	[[Category:Longevity]]		[[Category:Longevity]]

Andrea: expanded subsections

2022-11-12T19:33:49Z

expanded subsections

← Older revision		Revision as of 19:33, 12 November 2022
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	Autophagy (“''auto''” meaning “self”, and “''phagy''” meaning “to eat”) is a catabolic process highly conserved in eukaryotes, in which cytoplasmic components are delivered to the lysosome and degraded. It is a key process for the regulation of cellular energetic equilibrium and plays a housekeeping role by removing cellular waste, damaged organelles, aggregated or misfolded proteins and even intracellular pathogens.<ref name=":0" /><ref>Glick, D., Barth, S., & Macleod, K. (2010). Autophagy: cellular and molecular mechanisms. ''The Journal Of Pathology'', ''221''(1), 3-12. doi: 10.1002/path.2697</ref> The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.<ref>Maria Fimia, G., Stoykova, A., Romagnoli, A., Giunta, L., Di Bartolomeo, S., & Nardacci, R. et al. (2007). Ambra1 regulates autophagy and development of the nervous system. ''Nature'', ''447''(7148), 1121-1125. doi: 10.1038/nature05925</ref><ref>Qu, X., Zou, Z., Sun, Q., Luby-Phelps, K., Cheng, P., & Hogan, R. et al. (2007). Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. ''Cell'', ''128''(5), 931-946. doi: 10.1016/j.cell.2006.12.044</ref> The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0">Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, Bjedov I, Palikaras K, Simonsen A, Johansen T, Tavernarakis N, Rubinsztein DC, Partridge L, Kroemer G, Labbadia J, Fang EF. Autophagy in healthy aging and disease. Nat Aging. 2021 Aug;1(8):634-650. doi: 10.1038/s43587-021-00098-4. Epub 2021 Aug 12. PMID: 34901876; PMCID: PMC8659158.</ref>		Autophagy (“''auto''” meaning “self”, and “''phagy''” meaning “to eat”) is a catabolic process highly conserved in eukaryotes, in which cytoplasmic components are delivered to the lysosome and degraded. It is a key process for the regulation of cellular energetic equilibrium and plays a housekeeping role by removing cellular waste, damaged organelles, aggregated or misfolded proteins and even intracellular pathogens.<ref name=":0" /><ref>Glick, D., Barth, S., & Macleod, K. (2010). Autophagy: cellular and molecular mechanisms. ''The Journal Of Pathology'', ''221''(1), 3-12. doi: 10.1002/path.2697</ref> The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.<ref>Maria Fimia, G., Stoykova, A., Romagnoli, A., Giunta, L., Di Bartolomeo, S., & Nardacci, R. et al. (2007). Ambra1 regulates autophagy and development of the nervous system. ''Nature'', ''447''(7148), 1121-1125. doi: 10.1038/nature05925</ref><ref>Qu, X., Zou, Z., Sun, Q., Luby-Phelps, K., Cheng, P., & Hogan, R. et al. (2007). Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. ''Cell'', ''128''(5), 931-946. doi: 10.1016/j.cell.2006.12.044</ref> The connections between dysfunctional autophagy with aging and age-related diseases are abundant.<ref name=":0">Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, Bjedov I, Palikaras K, Simonsen A, Johansen T, Tavernarakis N, Rubinsztein DC, Partridge L, Kroemer G, Labbadia J, Fang EF. Autophagy in healthy aging and disease. Nat Aging. 2021 Aug;1(8):634-650. doi: 10.1038/s43587-021-00098-4. Epub 2021 Aug 12. PMID: 34901876; PMCID: PMC8659158.</ref>

	There are three well defined types of autophagy: ~~macro-autophagy~~, ~~micro-autophagy~~ and chaperone-mediated autophagy<ref>Parzych, K., & Klionsky, D. (2014). An Overview of Autophagy: Morphology, Mechanism, and Regulation. ''Antioxidants &Amp; Redox Signaling'', ''20''(3), 460-473. doi: 10.1089/ars.2013.5371</ref>, with chaperone-assisted selective autophagy (CASA) being recently added.<ref>Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11(3):538-46. doi: 10.1080/15548627.2015.1017186. PMID: 25714469; PMCID: PMC4502687.</ref><ref>Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010 Jan 26;20(2):143-8. doi: 10.1016/j.cub.2009.11.022. Epub 2010 Jan 7. PMID: 20060297.</ref> Despite differences in their mechanism of degradation and the molecular components they require, all three types of autophagy share in common the delivery of cytoplasmic cargo to the lysosome for proteolytic degradation. ~~Due~~ to ~~its role in disease~~, ~~macro~~-~~autophagy in particular has been the main focus of research over the past few decades~~, and ~~often the term “autophagy” is used to refer to the macro~~-~~autophagy type of autophagy~~.		=== Types of autophagy ===
			There are three well defined types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA)<ref>Parzych, K., & Klionsky, D. (2014). An Overview of Autophagy: Morphology, Mechanism, and Regulation. ''Antioxidants &Amp; Redox Signaling'', ''20''(3), 460-473. doi: 10.1089/ars.2013.5371</ref>, with chaperone-assisted selective autophagy (CASA) being recently added.<ref>Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11(3):538-46. doi: 10.1080/15548627.2015.1017186. PMID: 25714469; PMCID: PMC4502687.</ref><ref>Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010 Jan 26;20(2):143-8. doi: 10.1016/j.cub.2009.11.022. Epub 2010 Jan 7. PMID: 20060297.</ref> Despite differences in their mechanism of degradation and the molecular components they require, all three types of autophagy share in common the delivery of cytoplasmic cargo to the lysosome for proteolytic degradation. The different types of autophagy generally work in a coordinated manner to complement each other.<ref name=":1">Li, W.-wen, Li, J. and Bao, J.-ku (2011) “Microautophagy: Lesser-known self-eating,” ''Cellular and Molecular Life Sciences'', 69(7), pp. 1125–1136. Available at: <nowiki>https://doi.org/10.1007/s00018-011-0865-5</nowiki>.</ref>

	==== Mitophagy ====		==== Macroautophagy ====
	The selective degradation of ~~Mitochondria~~ through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref><references />		Due to its role in disease, macro-autophagy in particular has been the main focus of research over the past few decades, and often the term “autophagy” is used to refer to the macro-autophagy type of autophagy.<ref>Ichimiya, T. ''et al.'' (2020) “Autophagy and autophagy-related diseases: A Review,” ''International Journal of Molecular Sciences'', 21(23), p. 8974. Available at: <nowiki>https://doi.org/10.3390/ijms21238974</nowiki>.</ref>

			==== Microautophagy ====
			Microautophagy is a non-selective type of autophagy that involves the delivery of cyoplasmic cargo to the lysosome via autophagic tubes. Microautophagy can be induced under conditions of nitrogen restriction or [[rapamycin]].<ref name=":1" />

			Despite microautophagy being generally non-selective, there are three types of selected microautophagy that function in a selective manner: micropexophagy, piecemeal microautophagy of the nucleus (PMN) and micromitophagy.<ref name=":1" />

			==== Chaperone-mediated autophagy (CMA) ====
			Chaperone-mediate autophagy (CMA) is a type of autophagy that specifically engulfs cytosolic proteins, and thus plays an important role in the [[proteolysis]] pathway.<ref name=":2">Dice, J.F. (2007) “Chaperone-mediated autophagy,” ''Autophagy'', 3(4), pp. 295–299. Available at: <nowiki>https://doi.org/10.4161/auto.4144</nowiki>.</ref> It is estimated to be responsible for about 30% of protein degradation occurring during [[Calorie restriction\|caloric restriction]], and can also act under conditions of cellular oxidative stress. Similarly to the other types of autophagy, it requires transport of cytosolic cargo to the lysosomes, with the particularity that CMA binds to the LAMP-2A (lysosome-associated membrane protein type 2A) receptor located in the lysosomal membrane.<ref>Rout, A.K. ''et al.'' (2014) “Structure of transmembrane domain of lysosome-associated membrane protein type 2A (LAMP-2A) reveals key features for substrate specificity in chaperone-mediated autophagy,” ''Journal of Biological Chemistry'', 289(51), pp. 35111–35123. Available at: <nowiki>https://doi.org/10.1074/jbc.m114.609446</nowiki>.</ref> LAMP-2A protein together with a complex of chaperones and co-chaperones are essential for CMA and proteolysis pathways. The expression of LAMP-2A has been shown to decrease with aging, likely due to an age-related increased degradation of LAMP-2A and its decreased ability to insert itself into the lysosomal membrane.<ref name=":2" />

			==== Chaperone-assisted selective autophagy (CASA) ====

			==== Organelle-specific autophagy ====
			There are several types autophagy specific for certain organelles. Removal of damaged or overexpressed organelles is an essential mechanism for cellular quality control and systemic homeostasis.<ref name=":3">Yao, R.-Q. ''et al.'' (2020) “Organelle-specific autophagy in inflammatory diseases: A potential therapeutic target underlying the quality control of multiple organelles,” ''Autophagy'', 17(2), pp. 385–401. <nowiki>https://doi.org/10.1080/15548627.2020.1725377</nowiki>.</ref> A well studied specific subtype of autophagy is mitophagy (mitochondria). Other types include lysophagy (lysosomes), pexophagy (peroxisomes), reticulophagy (endoplasmic reticulum), ribophagy (ribosomes) and nucleophagy (nucleus).<ref name=":3" />

			===== Mitophagy =====
			The selective degradation of [[mitochondria]] through autophagy is known as mitophagy. There are multiple sub-types of mitophagy, such as PINK1/Parkin-dependant, Ubiquitin-independent receptor-mediated and others like piecemeal mitophagy.<ref>Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in Aging and Disease. Front Cell Dev Biol. 2020 Apr 15;8:239. doi: 10.3389/fcell.2020.00239. PMID: 32373609; PMCID: PMC7179682.</ref><references />
	[[Category:Longevity]]		[[Category:Longevity]]