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J Cell Sci. 2016 Jun 1;129(11):2170-81. doi: 10.1242/jcs.185165. Epub 2016 Apr 12.

Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission.

Author information

1
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia.
2
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3086, Australia.
3
Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, 3010, Australia.
4
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
5
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia Michael.Ryan@monash.edu.

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.

KEYWORDS:

Apoptosis; Dynamin-related protein 1; Fission; GTPase; Mitochondria

PMID:
27076521
DOI:
10.1242/jcs.185165
[Indexed for MEDLINE]
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