Autophagy-related Protein 32 Acts as Autophagic Degron and Directly Initiates Mitophagy

Abstract

Background: Atg32 is a transmembrane protein essential for mitochondria autophagy in yeast. Results: Atg32 harbors a module that is crucial for interactions with Atg8 and Atg11, and can even promote other organelle autophagy. Conclusion: Atg32 acts as a direct initiator at early stages of mitochondria autophagy. Significance: This might be a common molecular feature in mitochondria autophagy conserved from yeast to humans.

The LIR motif – crucial for selective autophagy

“…Atg32 can interact with Atg8 indirectly through Atg11 and directly through its LIR motif in the N-terminal cytosolic domain. Atg32 recruits Atg8 and Atg11 to the mitochondria surface to form an initiator complex essential for mitophagy (Kondo-Okamoto et al, 2012). In mammalian cells, three integral OMM proteins that all have a LIR motif in their cytosolic N-terminal domain are implicated in mitophagy (Fig.…”

Receptor-mediated mitophagy

“…The mutant cytosolic domain of Atg32 anchored to peroxisomes can promote peroxisome autophagy (pexophagy) [40]. Atg11 also interacts with Dnm1, a yeast homolog of Drp1, and the fission components are recruited to the mitochondria via this interaction [27].…”

“…A recent study revealed that casein kinase 2 has a pivotal role in Atg32 phosphorylation at Ser114 and Ser119 [39]. Atg32 mutants, which do not bind to Atg8 or Atg11, cannot induce mitochondrial degradation [16,17,40]. Furthermore,…”

Structural biology of the macroautophagy machinery

“…Selectivity is achieved by adaptor proteins that function to sequester specific components such as protein aggregates or whole organelles (Weidberg et al, 2011b;Suzuki, 2013). Various forms of selective autophagy have been named based on the recruited cargoes, with examples that include but not limited to, mitophagy (degradation of mitochondria, Kondo-Okamoto et al, 2012;Ashrafi and Schwarz, 2013), lipophagy, (degradation of lipids, Liu and Czaja, 2013) and ribophagy (degradation of ribosomes, Kraft et al, 2008). In comparison, nonselective autophagy has been characterized as a bulk degradation process, which functions independent of specialized cargo-receptor proteins.…”