title: Mitophagy in yeast is independent of mitochondrial fission and requires the stress response gene WHI2.
abstract: Dysfunctional mitochondria show a reduced capacity for fusion and, as mitochondrial fission is maintained, become spatially separated from the intact network. By that mechanism, dysfunctional mitochondria have been proposed to be targeted for selective degradation by mitophagy, thereby providing a quality control system for mitochondria. In yeast, conflicting results concerning the role of mitochondrial dynamics in mitophagy have been reported. Here, we investigate the effects on mitophagy of altering mitochondrial fission and fusion, using biochemical, as well as fluorescence-based, assays. Rapamycin-induced mitophagy was shown to depend upon the autophagy-related proteins Atg11, Atg20 and Atg24, confirming that a selective type of autophagy occurred. Both fragmentation of mitochondria and inhibition of oxidative phosphorylation were not sufficient to trigger mitophagy, and neither deletion of the fission factors Dnm1, Fis1, Mdv1 or Caf4 nor expression of dominant-negative variants of Dnm1 impaired mitophagy. The diminished mitophagy initially observed in a Δfis1 mutant was not due to the absence of Fis1 but rather due to a secondary mutation in WHI2, which encodes a factor reported to function in the general stress response and the Ras-protein kinase A (PKA) signaling pathway. We propose that, in yeast, mitochondrial fission is not a prerequisite for the selective degradation of mitochondria, and that mitophagy is linked to the general stress response and the Ras-PKA signaling pathway.
authors.affiliation: Adolf-Butenandt-Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5, 81377 München, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Mendl
authors.forename: Angelo
authors.initials: A
authors.lastname: Occhipinti
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.forename: Philipp
authors.initials: P
authors.lastname: Wild
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Reichert
mesh_terms: D000595:Amino Acid Sequence; D001343:Autophagy; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C470937:Whi2 protein, S cerevisiae