title: Mitochondrial-Shaping Proteins in Cardiac Health and Disease - the Long and the Short of It!
abstract: Mitochondrial health is critically dependent on the ability of mitochondria to undergo changes in mitochondrial morphology, a process which is regulated by mitochondrial shaping proteins. Mitochondria undergo fission to generate fragmented discrete organelles, a process which is mediated by the mitochondrial fission proteins (Drp1, hFIS1, Mff and MiD49/51), and is required for cell division, and to remove damaged mitochondria by mitophagy. Mitochondria undergo fusion to form elongated interconnected networks, a process which is orchestrated by the mitochondrial fusion proteins (Mfn1, Mfn2 and OPA1), and which enables the replenishment of damaged mitochondrial DNA. In the adult heart, mitochondria are relatively static, are constrained in their movement, and are characteristically arranged into 3 distinct subpopulations based on their locality and function (subsarcolemmal, myofibrillar, and perinuclear). Although the mitochondria are arranged differently, emerging data supports a role for the mitochondrial shaping proteins in cardiac health and disease. Interestingly, in the adult heart, it appears that the pleiotropic effects of the mitochondrial fusion proteins, Mfn2 (endoplasmic reticulum-tethering, mitophagy) and OPA1 (cristae remodeling, regulation of apoptosis, and energy production) may play more important roles than their pro-fusion effects. In this review article, we provide an overview of the mitochondrial fusion and fission proteins in the adult heart, and highlight their roles as novel therapeutic targets for treating cardiac disease.
authors.affiliation: Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore.|National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
authors.forename: Sang-Bing
authors.initials: SB
authors.lastname: Ong
authors.affiliation: The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Siavash Beikoghli
authors.initials: SB
authors.lastname: Kalkhoran
authors.affiliation: Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore.|National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
authors.forename: Sauri
authors.initials: S
authors.lastname: Hernández-Reséndiz
authors.affiliation: The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Parisa
authors.initials: P
authors.lastname: Samangouei
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Sang-Ging
authors.initials: SG
authors.lastname: Ong
authors.affiliation: Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore. derek.hausenloy@duke-nus.edu.sg.|National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore. derek.hausenloy@duke-nus.edu.sg.|The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK. derek.hausenloy@duke-nus.edu.sg.|The National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, UK. derek.hausenloy@duke-nus.edu.sg.
authors.forename: Derek John
authors.initials: DJ
authors.lastname: Hausenloy
mesh_terms: D000818:Animals; D017209:Apoptosis; D004734:Energy Metabolism; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D015398:Signal Transduction
chemical_list: D024101:Mitochondrial Proteins
keywords: Drp1; Ischemia/reperfusion injury; Mfn1; Mfn2; Mitochondrial fission; Mitochondrial fusion; Mitochondrial morphology; OPA1