Mitophagy Inducing Coumarin (MIC)

From Longevity Wiki
Mitophagy Inducing Coumarin (MIC)
Mitophagy Inducing Coumarin (MIC).jpg

Mitophagy Inducing Coumarin (MIC) is a benzocoumarin-based compound present in a high level in many edible plants and vegetables, which is capable of displaying a significant dose-dependent increase in TFEB (Transcription factor EB is a master gene for lysosomal biogenesis) promoter activity. MIC induces mitophagy and suppresses mitochondrial dysfunction, a major hallmark of aging, in both C. elegans and mammalian cell culture models.[1] Mechanistically, MIC acts by inhibiting ligand-induced activation of the nuclear hormone receptor DAF-12/FXR (Farnesoid X Receptor upstream regulator of HLH-30/TFEB), which, in turn, induces mitophagy and extends lifespan. A clinically relevant, structurally related mitophagy inducer, urolithin A, was found to also engage DAF-12/FXR signaling in a similar manner. However, unlike urolithin A, which is produced from ingested ellagitannins by gut bacteria whose levels decrease with age, MIC is a naturally-occurring constituent of many plants including numerous vegetables and essential oils[2]

  1. Chamoli, M., Rane, A., Foulger, A. et al. A drug-like molecule engages nuclear hormone receptor DAF-12/FXR to regulate mitophagy and extend lifespan. Nat Aging (2023).
  2. Chamoli, M., Rane, A., Chinta, S., Shahmirzadi, A., Kumsta, C., Nambiar, D., ... & Andersen, J. (2022). A drug-like molecule engages a nuclear hormone receptor to regulate mitophagy and promote mitochondrial mediated lifespan extension. :