title: Novel roles for actin in mitochondrial fission.
abstract: Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial contact generates the force required for pre-constriction or why pre-constriction leads to Drp1 recruitment. Recent results, however, show that ERMD might be an actin-based process in mammals that requires the ER-associated formin INF2 upstream of Drp1, and that myosin II and other actin-binding proteins might be involved. In this Commentary, we present a mechanistic model for mitochondrial fission in which actin and myosin contribute in two ways; firstly, by supplying the force for pre-constriction and secondly, by serving as a coincidence detector for Drp1 binding. In addition, we discuss the possibility that multiple fission mechanisms exist in mammals.
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Hatch
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Pinar S
authors.initials: PS
authors.lastname: Gurel
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA henry.higgs@dartmouth.edu.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Higgs
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D034281:Dynamins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000502:physiology*; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism
chemical_list: D000199:Actins; D009218:Myosins; D034281:Dynamins
keywords: Actin; Mitochondrial fission; Myosin