title: Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis.
abstract: Macromitophagy controls mitochondrial quality and quantity. It involves the sequestration of dysfunctional or excessive mitochondria within double-membrane autophagosomes, which then fuse with the vacuole/lysosome to deliver these mitochondria for degradation. To investigate a physiological role of macromitophagy in yeast, we examined how theatg32Δ-dependent mutational block of this process influences the chronological lifespan of cells grown in a nutrient-rich medium containing low (0.2%) concentration of glucose. Under these longevity-extending conditions of caloric restriction (CR) yeast cells are not starving. We also assessed a role of macromitophagy in lifespan extension by lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR conditions. Our findings imply that macromitophagy is a longevity assurance process underlying the synergistic beneficial effects of CR and LCA on yeast lifespan. Our analysis of how the atg32Δ mutation influences mitochondrial morphology, composition and function revealed that macromitophagy is required to maintain a network of healthy mitochondria. Our comparative analysis of the membrane lipidomes of organelles purified from wild-type and atg32Δ cells revealed that macromitophagy is required for maintaining cellular lipid homeostasis. We concluded that macromitophagy defines yeast longevity by modulating vital cellular processes inside and outside of mitochondria.
authors.affiliation: Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada.
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Richard
authors.forename: Anna
authors.initials: A
authors.lastname: Leonov
authors.forename: Adam
authors.initials: A
authors.lastname: Beach
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Burstein
authors.forename: Olivia
authors.initials: O
authors.lastname: Koupaki
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gomez-Perez
authors.forename: Sean
authors.initials: S
authors.lastname: Levy
authors.forename: Lukas
authors.initials: L
authors.lastname: Pluska
authors.forename: Sevan
authors.initials: S
authors.lastname: Mattie
authors.forename: Rami
authors.initials: R
authors.lastname: Rafesh
authors.forename: Tatiana
authors.initials: T
authors.lastname: Iouk
authors.forename: Sara
authors.initials: S
authors.lastname: Sheibani
authors.forename: Michael
authors.initials: M
authors.lastname: Greenwood
authors.forename: Hojatollah
authors.initials: H
authors.lastname: Vali
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Titorenko
mesh_terms: D000818:Animals; D003470:Culture Media / Q000494:pharmacology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D003470:Culture Media
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