New perspectives on the role of Drp1 isoforms in regulating mitochondrial pathophysiology

Ayeshah A. Rosdah, William J. Smiles, Jonathan S. Oakhill, John W. Scott, Christopher G. Langendorf, Lea M.D. Delbridge, Jessica K. Holien, Shiang Y. Lim

Research output: Contribution to journalReview ArticleResearchpeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Article number107594
Number of pages16
JournalPharmacology and Therapeutics
Volume213
DOIs
Publication statusPublished - Sep 2020
Externally publishedYes

Keywords

  • cell survival
  • Drp1
  • isoforms
  • mitochondrial function
  • mitochondrial morphology

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