Atg32 Is a Mitochondrial Protein that Confers Selectivity during Mitophagy

Abstract

Mitochondrial quality control is important to maintain proper cellular homeostasis. Although selective mitochondrial degradation by autophagy (mitophagy) is suggested to have an important role for quality control and there is evidence for a direct relation between mitophagy and neurodegenerative diseases, the molecular mechanism of mitophagy is poorly understood. Using a screen for mitophagy-deficient mutants, we found that YIL146C/ECM37 is essential for mitophagy. This gene is not required for other types of selective autophagy or for nonspecific macroautophagy. We designated this autophagy-related (ATG) gene as ATG32. The Atg32 protein localizes on mitochondria. Following the induction of mitophagy, Atg32 binds Atg11, an adaptor protein for selective types of autophagy, and then Atg32 is recruited to and imported into the vacuole along with mitochondria. Therefore, Atg32 confers selectivity for mitochondrial sequestration as a cargo and is necessary for recruitment of this organelle by the autophagy machinery for mitophagy.

NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy

“…After 6-7 h, cells were harvested and analyzed for release of free GFP, indicative of mitophagy. [18][19][20][21][22][23][24] The free GFP band was apparent beginning at 6 h after induction of mitophagy in w/t cells, and was markedly decreased in ndk1Δ cells, indicating the impaired Figure 10). These findings suggest that Ndk1/Ynk1 is an important contributor to the elimination of mitochondria induced by starvation of yeast cells.…”

Autophagy at the crossroads of catabolism and anabolism

“…For example, damaged and superfluous mitochondria are targeted to autophagosomes in a process termed mitophagy 24,25 . Numerous studies have led to the identification of mitophagy receptors such as Atg32 in yeast, as well as BCL2/adenovirus E1B 19 kDa proteininteracting protein 3 (BNIP3), NIP3-like protein X (NIX) and FUN14 domain-containing protein 1 (FUNDC1) in mammals [26][27][28][29][30][31][32][33] . These receptors all possess an LIR motif to directly target mitochondria to autophagosomes.…”

Role of plant autophagy in stress response

“…To date, the number of ATG genes has increased to 32 (Barth et al, 2001;Klionsky et al, 2003;Kanki et al, 2009;Nakatogawa et al, 2009;Okamoto et al, 2009). Homologues to the yeast ATG genes have been found in mammals and plants, which indicates the conservation of the core ATG mechanism during evolution.…”