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New perspectives on the role of Drp1 isoforms in regulating mitochondrial pathophysiology
Rosdah, Ayeshah A. Smiles, William J. Oakhill, Jonathan S. Scott, John W. Langendorf, Christopher G. Delbridge, Lea M. D. Holien, Jessica K. Lim, Shiang Y.
Rosdah, Ayeshah A.
Smiles, William J.
Oakhill, Jonathan S.
Scott, John W.
Langendorf, Christopher G.
Delbridge, Lea M. D.
Holien, Jessica K.
Lim, Shiang Y.
Abstract
Mitochondria are dynamic organelles constantly undergoing fusion and fission. A concerted balance between the process of mitochondrial fusion and fission is required to maintain cellular health under different physiological conditions. Mutation and dysregulation of Drp1, the major driver of mitochondrial fission, has been associated with various neurological, oncological and cardiovascular disorders. Moreover, when subjected to pathological insults, mitochondria often undergo excessive fission, generating fragmented and dysfunctional mitochondria leading to cell death. Therefore, manipulating mitochondrial fission by targeting Drp1 has been an appealing therapeutic approach for cytoprotection. However, studies have been inconsistent. Studies employing Drp1 constructs representing alternate Drp1 isoforms, have demonstrated differing impacts of these isoforms on mitochondrial fission and cell death. Furthermore, there are distinct expression patterns of Drp1 isoforms in different tissues, suggesting idiosyncratic engagement in specific cellular functions. In this review, we will discuss these inherent variations among human Drp1 isoforms and how they could affect Drp1-mediated mitochondrial fission and cell death.
Keywords
Drp1, isoforms, mitochondrial morphology, mitochondrial function, cell survival
Date
2020
Type
Journal article
Journal
Pharmacology and Therapeutics
Book
Volume
213
Issue
Page Range
1-16
Article Number
Article 107594
ACU Department
Non-faculty
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
All rights reserved
File Access
Controlled