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The constriction and scission machineries involved in mitochondrial fission

ABSTRACT A key event in the evolution of eukaryotic cells was the engulfment of an aerobic bacterium by a larger anaerobic archaebacterium, leading to a close relationship between the host and the newly formed endosymbiont. Mitochondria, originating from this event, have evolved to be the main place of cellular ATP production. Maintaining elements of their independence, mitochondria undergo growth and division in the cell, thereby ensuring that new daughter cells inherit a mitochondrial complement. Mitochondrial division is also important for other processes, including quality control, mitochondrial (mt)DNA inheritance, transport and cell death. However, unlike bacterial fission, which uses a dynamin-related protein to constrict the membrane at its inner face, mitochondria use dynamin and dynamin-related proteins to constrict the outer membrane from the cytosolic face. In this Review, we summarize the role of proteins from the dynamin superfamily in mitochondrial division. This includes recent findings highlighting that dynamin-2 (Dnm2) is involved in mitochondrial scission, which led to the reappraisal of the role of dynamin-related protein 1 (Drp1; also known as Dnm1l) and its outer membrane adaptors as components of the mitochondrial constriction machinery along with ER components and actin. Summary: In this Review, we outline the machinery involved in mitochondrial fission including the recent discovery of Dnm2 as the final executor of membrane scission. An updated model of fission is presented.