Glutathione participates in the regulation of mitophagy in yeast.
The antioxidant N-acetyl-l-cysteine prevented the autophagy-dependent delivery of mitochondria to the vacuoles, as examined by fluorescence microscopy of mitochondria-targeted green fluorescent protein, transmission electron microscopy, and Western blot analysis of mitochondrial proteins. The effect of N-acetyl-l-cysteine was specific to mitochondrial autophagy (mitophagy). Indeed, autophagy-dependent activation of alkaline phosphatase and the presence of hallmarks of non-selective microautophagy were not altered by N-acetyl-l-cysteine. The effect of N-acetyl-l-cysteine was not related to its scavenging properties, but rather to its fueling effect of the glutathione pool. As a matter of fact, the decrease of the glutathione pool induced by chemical or genetical manipulation did stimulate mitophagy but not general autophagy. Conversely, the addition of a cell-permeable form of glutathione inhibited mitophagy. Inhibition of glutathione synthesis had no effect in the strain Deltauth1, which is deficient in selective mitochondrial degradation. These data show that mitophagy can be regulated independently of general autophagy, and that its implementation may depend on the cellular redox status.
Deffieu
Maika
M
CNRS, Institut de Biochimie et de Génétique Cellulaires (UMR 5095), Université de Bordeaux 2, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
Bhatia-Kissová
Ingrid
I
Salin
Bénédicte
B
Galinier
Anne
A
Manon
Stéphen
S
Camougrand
Nadine
N
D000111:Acetylcysteine / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D003470:Culture Media; D004976:Ethacrynic Acid / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D009584:Nitrogen / Q000172:deficiency; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D003470:Culture Media; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C116477:UTH1 protein, S cerevisiae; D049452:Green Fluorescent Proteins; D005978:Glutathione; D004976:Ethacrynic Acid; D009584:Nitrogen; D000111:Acetylcysteine