Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast.
Autophagy, a highly regulated programme found in almost all eukaryotes, is mainly viewed as a catabolic process that degrades nonessential cellular components into molecular building blocks, subsequently available for biosynthesis at a lesser expense than de novo synthesis. Autophagy is largely known to be regulated by nutritional conditions. Here we show that, in yeast cells grown under nonstarving conditions, autophagy can be induced by mitochondrial dysfunction. Electron micrographs and biochemical studies show that an autophagic activity can result from impairing the mitochondrial electrochemical transmembrane potential. Furthermore, mitochondrial damage-induced autophagy results in the preferential degradation of impaired mitochondria (mitophagy), before leading to cell death. Mitophagy appears to rely on classical macroautophagy machinery while being independent of cellular ATP collapse. These results suggest that in this case, autophagy can be envisioned either as a process of mitochondrial quality control, or as an ultimate cellular response triggered when cells are overwhelmed with damaged mitochondria.
Priault
M
M
Département de Biologie Cellulaire, Université de Genève, Suisse. muriel.priault@univ-nantes.fr
Salin
B
B
Schaeffer
J
J
Vallette
F M
FM
di Rago
J-P
JP
Martinou
J-C
JC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases