Autophagy

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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.[1][2] The process of autophagy is also critical in several developmental processes and in response to nutrient stresses.[3][4] The connections between dysfunctional autophagy with aging and age-related diseases are abundant.[1]

There are three well defined types of autophagy: macro-autophagy, micro-autophagy and chaperone-mediated autophagy[5], with chaperone-assisted selective autophagy (CASA) being recently added.[6][7] 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.

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.[8]

  1. 1.0 1.1 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.
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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.
  7. 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.
  8. 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.