Mitochondrial fusion and fission dynamics are fundamental to a number of cellular processes, including the regulation of apoptosis, neurodegeneration and aging. It has been proposed that dysfunctional mitochondria, which show a reduced capacity for fusion, are selectively degraded (a process called mitophagy). The molecular mechanism of mitophagy, however, has remained elusive, and there are conflicting data regarding the involvement of mitochondrial fission. Here, Ivan Dikic, Andreas S. Reichert and colleagues (p. 1339) characterise the mitophagy response in yeast in the context of mitochondrial dynamics. The authors show that rapamycin-induced mitophagy is a selective form of autophagy. Mitophagy is not triggered by mitochondrial fragmentation or inhibition of oxidative phosphorylation, nor is it impaired by the deletion of components of the mitochondrial fission machinery (e.g. Dnm1 or Fis1) or the expression of dominant-negative variants of Dnm1. Interestingly, the impaired mitophagy observed in a fis1 deletion strain is not caused by the absence of Fis1, but rather by a secondary mutation in the stress-response gene Whiskey 2. The authors propose, therefore, that mitochondrial fission is not a prerequisite for autophagy in yeast, nor is it sufficient to induce mitophagy; in fact, mitophagy may be linked to the stress response and the related Ras–protein-kinase-A signalling pathway.
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