Abstract

Research into the selective autophagic degradation of mitochondria—mitophagy—has intensified in recent years, yielding significant insights into the function, mechanism, and regulation of this process in the eukaryotic cell. However, while some molecular players in budding yeast, such as Atg32p, Uth1p, and Aup1p, have been identified, studies further interrogating the mechanistic and regulatory features of mitophagy have yielded inconsistent and sometimes conflicting results. In this review, we focus on the current understanding of mitophagy mechanism, induction, and regulation in yeast, and suggest that differences in experimental conditions used in the various studies of mitophagy may contribute to the observed discrepancies. Consideration and understanding of these differences may help place the mechanism and regulation of mitophagy in context, and further indicate the intricate role that this essential process plays in the life and death of eukaryotic cells.

Highlights

  • Even within large multicellular organisms, cells are not guaranteed a life within completely stable tissue environments

  • Following a brief overview of the signalling pathways known to be involved in the regulation of this process, we identify and discuss discrepancies in the literature with reference to the diversity of mitochondrial stresses, and how the cell coordinates its response to bring about mitophagy

  • It is interesting to note, that target of rapamycin (TOR) signalling regulated the localisation and activity of Rtg3p, suggesting a link between nitrogen sensing and mitophagy [92]. These findings suggest that the mitochondrion is not a passive subject of mitophagy; rather, mitochondria appear to play an active role in the regulation of their own removal by mitophagy

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Summary

Introduction

Even within large multicellular organisms, cells are not guaranteed a life within completely stable tissue environments. The highly conserved process of autophagy is an important adaptation to the diverse challenges presented by environments in which unicellular and multicellular eukaryotic cells exist. This process involves the transport of cellular components to the lysosome (in mammals) or vacuole (yeast) for degradation to fundamental components that are recycled by the cell. In recent years, both nonselective and selective forms of autophagy, the uptake of bulk, random portions of the cytosol, or of specific targets, respectively, have been described. Discrepancies apparent in research undertaken to date will be addressed with reference to the experimental conditions employed in these studies and their relationship to our current understanding of mitophagy

Autophagy and Mitophagy as Unique Forms of Intracellular Degradation
Mitophagy as a Response to Stress
Regulation of Mitophagy
Mitophagy Mechanism and Regulation
Conclusion
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