Mitochondrial fission is a homeostatic process that can lead to either the formation of new mitochondria or the removal of damaged ones by mitophagy. Here, Suliana Manley and colleagues ask how these two fate decisions are distinguished. Using high-resolution imaging of live cells, they observe two functionally and mechanistically distinct types of fission. Specifically, when the mitochondrial fission site is at the periphery of the organelle, the resulting smaller daughter mitochondrion is cleared by mitophagy. By contrast, fission at the midzone leads to mitochondrial proliferation. Both types of fission event involve dynamin-related protein 1 (DRP1), but the distinction comes at the level of different membrane adaptor proteins that recruit DRP1. Moreover, only midzone fission involves pre-constriction mediated by actin and the endoplasmic reticulum.
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