Molecular mechanism and physiological functions of mitophagy in yeast

Abstract

In eukaryotic cells, mitochondria serve as the central source of cellular energy. As a byproduct of energy production, mitochondria also generate reactive oxygen species. Because accumulation of oxidative damage causes diverse pathologies, cells must maintain a proper pool of functional mitochondria in response to energetic demands and various stimuli. Selective removal of mitochondria by autophagy, called mitophagy, is thought to contribute to elimination of excess or dysfunctional mitochondria to maintain mitochondrial homeostasis. Mitophagy is a catabolic process where a part of mitochondria is engulfed into double-membrane vesicles termed autophagosomes, which then fuse with lysosomes/vacuoles, resulting in cargo degradation by lysosomal/vacuolar proteases. Studies using the budding yeast Saccharomyces cerevisiae as a model organism have significantly contributed to the understating of the mechanism, regulation, and functional roles of mitophagy. In S. cerevisiae, Atg32, a mitochondrial surface protein, is a key molecule in mitophagy, serving as a mitophagy receptor that connects a part of mitochondria to the autophagy machinery through its direct interaction with autophagy proteins required for autophagosome formation. Mitophagy induction in yeast is tightly controlled through transcriptional and post-translational regulations of Atg32. Furthermore, physiological functions of mitophagy have been explored using cells deleted for Atg32 as mitophagy-deficient mutants since Atg32 is a mitophagy-specific protein. In this review, by focusing on yeast mitophagy, we overview recent advances in our understanding of the molecular mechanism and physiological functions of autophagic degradation of mitochondria.