Mitophagy in yeast: known unknowns and unknown unknowns

Abstract

Mitophagy, the autophagic breakdown of mitochondria, is observed in eukaryotic cells under various different physiological circumstances. These can be broadly categorized into two types: mitophagy related to quality control events and mitophagy induced during developmental transitions. Quality control mitophagy involves the lysosomal or vacuolar degradation of malfunctioning or superfluous mitochondria within lysosomes or vacuoles, and this is thought to serve as a vital maintenance function in respiring eukaryotic cells. It plays a crucial role in maintaining physiological balance, and its disruption has been associated with the progression of late-onset diseases. Developmentally induced mitophagy has been reported in the differentiation of metazoan tissues which undergo metabolic shifts upon developmental transitions, such as in the differentiation of red blood cells and muscle cells. Although the mechanistic studies of mitophagy in mammalian cells were initiated after the initial mechanistic findings in Saccharomyces cerevisiae, our current understanding of the physiological role of mitophagy in yeast remains more limited, despite the presence of better-defined assays and tools. In this review, I present my perspective on our present knowledge of mitophagy in yeast, focusing on physiological and mechanistic aspects. I aim to focus on areas where our understanding is still incomplete, such as the role of mitochondrial dynamics and the phenomenon of protein-level selectivity.