• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
              Advocacy & Research for Unlimited Lifespans


PAYWALLED > Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis

mitochondria lysosome vacuole iron aging yeast amino acid cysteine v-atpase

  • Please log in to reply
No replies to this topic

#1 Engadin

  • Guest
  • 197 posts
  • 569
  • Location:Madrid
  • NO

Posted 24 January 2020 - 10:20 PM







P A Y W A L L E D    S O U R C E :   Cell






  •  Elevated cysteine disrupts mitochondrial respiration in vacuole-impaired cells
  •  Cysteine inhibits mitochondrial function by limiting iron bioavailability
  •  Vacuoles sequester cysteine to promote efficient mitochondrial respiration
  •  Cysteine restriction or iron supplementation sustains mitochondrial health in aging
Mitochondria and lysosomes are functionally linked, and their interdependent decline is a hallmark of aging and disease. Despite the long-standing connection between these organelles, the function(s) of lysosomes required to sustain mitochondrial health remains unclear. Here, working in yeast, we show that the lysosome-like vacuole maintains mitochondrial respiration by spatially compartmentalizing amino acids. Defects in vacuole function result in a breakdown in intracellular amino acid homeostasis, which drives age-related mitochondrial decline.
Among amino acids, we find that cysteine is most toxic for mitochondria and show that elevated non-vacuolar cysteine impairs mitochondrial respiration by limiting intracellular iron availability through an oxidant-based mechanism. Cysteine depletion or iron supplementation restores mitochondrial health in vacuole-impaired cells and prevents mitochondrial decline during aging. These results demonstrate that cysteine toxicity is a major driver of age-related mitochondrial deterioration and identify vacuolar amino acid compartmentation as a cellular strategy to minimize amino acid toxicity.

Edited by Engadin, 24 January 2020 - 10:23 PM.

  • Informative x 1

Also tagged with one or more of these keywords: mitochondria, lysosome, vacuole, iron, aging, yeast, amino acid, cysteine, v-atpase

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users