Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission
Laura D. Osellame,Abeer P. Singh,Abeer P. Singh,David A. Stroud,Catherine S Palmer,Diana Stojanovski,Rajesh Ramachandran,Michael T. Ryan +7 more
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TLDR
MiD51 and Mff coordinate and regulate the action of Drp1 at the mitochondrial outer membrane during homeostatic mitochondrial fission, as assessed with gene-editing technology.Abstract:
Cytosolic dynamin-related protein 1 (Drp1, also known as DNM1L) is required for both mitochondrial and peroxisomal fission. Drp1-dependent division of these organelles is facilitated by a number of adaptor proteins at mitochondrial and peroxisomal surfaces. To investigate the interplay of these adaptor proteins, we used gene-editing technology to create a suite of cell lines lacking the adaptors MiD49 (also known as MIEF2), MiD51 (also known as MIEF1), Mff and Fis1. Increased mitochondrial connectivity was observed following loss of individual adaptors, and this was further enhanced following the combined loss of MiD51 and Mff. Moreover, loss of adaptors also conferred increased resistance of cells to intrinsic apoptotic stimuli, with MiD49 and MiD51 showing the more prominent role. Using a proximity-based biotin labeling approach, we found close associations between MiD51, Mff and Drp1, but not Fis1. Furthermore, we found that MiD51 can suppress Mff-dependent enhancement of Drp1 GTPase activity. Our data indicates that Mff and MiD51 regulate Drp1 in specific ways to promote mitochondrial fission.read more
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Mitochondrial dynamics: overview of molecular mechanisms
TL;DR: An overview of the molecular mechanisms that govern mitochondrial fission and fusion in mammals is described and several members of the machinery can undergo post-translational modifications modulating these processes.
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hFis1, a novel component of the mammalian mitochondrial fission machinery. Vol. 278 (2003) 36373–36379
TL;DR: In this article, the authors identified a mammalian protein called hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division, and when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission.
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The cell biology of mitochondrial membrane dynamics
TL;DR: How bioenergetics and cellular signalling are linked to dynamic changes of mitochondrial morphology is described, with morphological changes to mitochondria accompanying a multitude of processes as diverse as cell pluripotency, division, differentiation, senescence and death.
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Here, there, and everywhere: The importance of ER membrane contact sites
TL;DR: It's all about your contacts Membrane contact sites have recently come to the fore of the understanding of interorganelle communication and how these important structures help to promote a variety of key functions, including organelle division and lipid transfer.
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Multiple dynamin family members collaborate to drive mitochondrial division
TL;DR: The ubiquitously expressed classical dynamin-2 (Dyn2) is a fundamental component of the mitochondrial division machinery and a combination of live-cell and electron microscopy in three different mammalian cell lines reveals that Dyn2 works in concert with Drp1 to orchestrate sequential constriction events that build up to division.
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