Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alters metabolism, proliferation, apoptosis and mitophagy, contributing to human diseases, including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), cancer and ischemia/reperfusion injury. Post-translational regulation of Drp1 (by phosphorylation and SUMOylation) is an established means of modulating Drp1 activation and translocation to the outer mitochondrial membrane (OMM). This review focuses on Drp1 adaptor proteins that also regulate fission. The proteins include fission 1 (Fis1), mitochondrial fission factor (Mff) and mitochondrial dynamics proteins of 49 kDa and 51 kDa (MiD49, MiD51). Heterologous MiD overexpression sequesters inactive Drp1 on the OMM, promoting fusion; conversely, increased endogenous MiD creates focused Drp1 multimers that optimize OMM scission. The triggers that activate MiD-bound Drp1 in disease states are unknown; however, MiD51 has a unique capacity for ADP binding at its nucleotidyltransferase domain. Without ADP, MiD51 inhibits Drp1, whereas ADP promotes MiD51-mediated fission, suggesting a link between metabolism and fission. Confusion over whether MiDs mediate fusion (by sequestering inactive Drp1) or fission (by guiding Drp1 assembly) relates to a failure to consider cell types used and to distinguish endogenous compared with heterologous changes in expression. We speculate that endogenous MiDs serve as Drp1-binding partners that are dysregulated in disease states and may be important targets for inhibiting cell proliferation and ischemia/reperfusion injury. Moreover, it appears that the composition of the fission apparatus varies between disease states and amongst individuals. MiDs may be important targets for inhibiting cell proliferation and attenuating ischemia/reperfusion injury.
Skip Nav Destination
Article navigation
November 2016
-
Cover Image
Cover Image
The effect on lung function and respiratory symptoms of reducing of consumption of conventional cigarettes by switching to electronic cigarettes is investigated by the Cibella et al. in their Clinical Science research article on pages 1929-1937 (volume 130, issue 21).
Review Article|
September 22 2016
The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease
Kathleen Atkins;
Kathleen Atkins
1
*Department of Medicine, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Search for other works by this author on:
Asish Dasgupta;
Asish Dasgupta
1
*Department of Medicine, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Search for other works by this author on:
Kuang-Hueih Chen;
Kuang-Hueih Chen
*Department of Medicine, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Search for other works by this author on:
Jeff Mewburn;
Jeff Mewburn
*Department of Medicine, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Search for other works by this author on:
Stephen L. Archer
*Department of Medicine, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Correspondence: Professor Stephen L. Archer (email stephen.archer@queensu.ca).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 14 2016
Revision Received:
July 11 2016
Accepted:
July 26 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (21): 1861–1874.
Article history
Received:
January 14 2016
Revision Received:
July 11 2016
Accepted:
July 26 2016
Citation
Kathleen Atkins, Asish Dasgupta, Kuang-Hueih Chen, Jeff Mewburn, Stephen L. Archer; The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease. Clin Sci (Lond) 1 November 2016; 130 (21): 1861–1874. doi: https://doi.org/10.1042/CS20160030
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.