OPA1 regulation of mitochondrial dynamics in skeletal and cardiac muscle

John Noone; Donal J O'Gorman; Helena C Kenny

doi:10.1016/j.tem.2022.07.003

OPA1 regulation of mitochondrial dynamics in skeletal and cardiac muscle

Trends Endocrinol Metab. 2022 Oct;33(10):710-721. doi: 10.1016/j.tem.2022.07.003. Epub 2022 Aug 6.

Authors

John Noone¹, Donal J O'Gorman², Helena C Kenny³

Affiliations

¹ 3U Diabetes Partnership, School of Health and Human Performance, Dublin City University, Dublin, Ireland; National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin, Ireland; Translational Research Institute, AdventHealth, Orlando, FL, USA.
² 3U Diabetes Partnership, School of Health and Human Performance, Dublin City University, Dublin, Ireland; National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland; SSPC, The SFI Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Limerick, Ireland. Electronic address: donal.ogorman@dcu.ie.
³ Division of Endocrinology and Metabolism, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.

PMID: 35945104
DOI: 10.1016/j.tem.2022.07.003

Abstract

The mitochondria are double-membrane organelles integral for energy metabolism. Mitochondrial dynamics is regulated by inner and outer mitochondrial membrane (IMM and OMM) proteins, which promote fission and fusion. Optic atrophy 1 (OPA1) regulates IMM fusion, prevents apoptosis, and is a key regulator of morphological change in skeletal and cardiac muscle physiology and pathophysiology. OPA1 fuses the inner membranes of adjacent mitochondria, allowing for an increase in oxidative phosphorylation (OXPHOS). Considering the importance of energy metabolism in whole-body physiology, OPA1 and its regulators have been proposed as novel targets for the treatment of skeletal muscle atrophy and heart failure. Here, we review the role and regulation of OPA1 in skeletal muscle and cardiac pathophysiology, epitomizing its critical role in the cell.

Keywords: exercise; heart; metabolism; mitochondria; skeletal muscle.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

GTP Phosphohydrolases* / genetics
GTP Phosphohydrolases* / metabolism
Humans
Mitochondria / metabolism
Mitochondrial Dynamics*
Mitochondrial Membranes / metabolism
Mitochondrial Proteins / metabolism
Muscle, Skeletal* / metabolism
Myocardium* / metabolism

Substances

Mitochondrial Proteins
GTP Phosphohydrolases
OPA1 protein, human