Cited by 336Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

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

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Osellame, Laura D., Singh, Abeer P., Stroud, David A., Palmer, Catherine S., Stojanovski, Diana, Ramachandran, Rajesh, Ryan, Michael T.·2016·Journal of Cell Science

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.

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Crossref · 10.1242/jcs.185165

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Authors
Osellame, L. D., Singh, A. P., Stroud, D. A., Palmer, C. S., Stojanovski, D., Ramachandran, R., & Ryan, M. T.
Affiliations
  • Monash University (AU)
  • La Trobe University (AU)
  • Burnet Institute (AU)
  • The University of Melbourne (AU)
  • Case Western Reserve University (US)
Venue
Journal of Cell Science
Published
2016-06-01
Volume
129
Issue
11
Pages
2170-2181
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W2415256624
Cited by
336
References
63
Citations by year
2026: 18 · 2025: 34 · 2024: 28 · 2023: 30 · 2022: 35 · 2021: 48 · 2020: 36 · 2019: 31 · 2018: 37 · 2017: 29 · 2016: 9
FWCI
18.36
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Health and Medical Research Council (1049968)
  • American Heart Association (13BGIA14810010)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
mitochondrial fission, Drp1, Mff, MiD51, Fis1, apoptosis resistance, protein-protein interaction
MeSH terms
Gene Editing, Animals, Cell Line, Membrane Proteins, Mice, Inbred C57BL, Staining and Labeling, Cell Death, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Peroxisomes, Mitochondrial Proteins, Dynamins, Mitochondrial Dynamics

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