OPA1 in Cardiovascular Health and Disease

Burke, Niall; Hall, Andrew; Hausenloy, Derek J.

doi:10.2174/1389450116666150102113648

Cited by 16 publications

(13 citation statements)

References 60 publications

(87 reference statements)

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“…According to the summary, we find that under I/R conditions, the actions of mitochondrial fusion proteins on cardiomyocyte apoptosis are tightly associated with the underlying mechanisms. Mitochondrial fusion proteins have fusion effects and non‐fusion effects (Burke, Hall, & Hausenloy, ; Ong et al, ). The protective effects of fusion proteins on cardiomyocytes upon I/R depend on their fusion effects.…”

Section: The Role Of Mitochondrial Fusion and Fission In Cardiomyocytmentioning

confidence: 99%

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Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

2018

Journal Cellular Physiology

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As the main source of energy in the body, mitochondria are highly dynamic organelles, which are constantly going through fusion and fission. The fine balance of mitochondrial fusion and fission plays an important role in maintaining the stability of cardiomyocyte homeostasis. The processes of mitochondrial fusion and fission are very complex, which is mediated by fusion and fission proteins. Disruptions in these processes through controlling fusion and fission proteins affect mitochondrial functions and cardiomyocyte survival. Ischemia/reperfusion (I/R) can regulate the expression and post‐translational modifications of fusion and fission proteins thereby inducing the abnormality of mitochondrial fusion and fission and cardiomyocyte apoptosis. Furthermore, intervention with the expression and function of fusion and fission proteins influences on cardiomyocyte apoptosis under I/R conditions. In this review, we focus on the current developments in the effects of mitochondrial fusion and fission on cardiomyocyte functions, the implications for cardiomyocyte apoptosis in response to I/R, and possible mechanisms. And we review their roles as a potential therapeutic target for treating I/R‐induced cardiomyocyte injury.

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Section: The Role Of Mitochondrial Fusion and Fission In Cardiomyocytmentioning

confidence: 99%

“…Mitochondrial fusion proteins have fusion effects and non-fusion effects (Burke, Hall, & Hausenloy, 2015;. The protective effects of fusion proteins on cardiomyocytes upon I/R depend on their fusion effects.…”

Section: Mitochondrial Fusion and Apoptosis Induced By I/rmentioning

confidence: 99%

Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

2018

Journal Cellular Physiology

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“…The activity of the IMM pro-fusion protein OPA1 is regulated by alternative splicing and post-translational modification (for a more detailed review please see [112]). In addition to its pro-fusion effects OPA1 has been demonstrated to display a number of pleiotropic non-fusion effects.…”

Section: Mitochondrial Fusion Proteinsmentioning

confidence: 99%

“…In this regard, the discovery of other components of the mitochondrial fission machinery such as ER-mediated mitochondrial pre-constriction and the Drp1 docking proteins in the OMM, Mff and MiD49/51, may provide novel therapeutic targets for inhibiting mitochondrial fission. It is important to appreciate that although acute inhibition of mitochondrial fission induced by acute IRI is cardioprotective, the chronic inhibition of Drp1 may be detrimental to the heart as the process of mitochondrial fission is necessary for the removal of damaged mitochondria by mitophagy [112, 196]. This was nicely illustrated by Ikeda et al [83] who demonstrated that conditional cardiac-specific ablation of Drp1 induced mitochondrial elongation, suppressed mitophagy, increased MPTP opening susceptibility, resulting in a cardiomyopathy and increased MI size following acute IRI.…”

Section: Mitochondrial Fusion and Fission Proteins In Cardiac Health mentioning

confidence: 99%

Mitochondrial-Shaping Proteins in Cardiac Health and Disease – the Long and the Short of It!

Ong

Kalkhoran

Hernández‐Reséndiz

et al. 2017

Cardiovasc Drugs Ther

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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.

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“…Consequently, these and other studies have inspired an interest in developing strategies to regulate Opa1 expression and function; for a comprehensive account of Opa1 as a therapeutic target in the heart, see Burke et al . (). Cleavage of Opa1‐L to form Opa1‐S with removal of the transmembrane anchor occurs under stress conditions in response to pro‐apoptotic stimuli, loss of membrane potential and drop in ATP levels (Baricault et al, ).…”

Section: Electron Tomography and Mitochondrial Membrane Structurementioning

confidence: 97%

Three‐dimensional electron microscopy techniques for unravelling mitochondrial dysfunction in heart failure and identification of new pharmacological targets

Daghistani

Rajab

Kitmitto

2018

British J Pharmacology

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A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fundamental for the current understanding of mitochondrial structure–function, (ii) the paradigm shift in resolutions now achievable by 3‐D EM techniques due to the introduction of direct detection devices and phase plate technology, and (iii) the application of EM for unravelling mitochondrial pathological remodelling in heart failure. We further consider the tremendous potential of multi‐scale EM techniques for the development of therapeutics, structure‐based ligand design and for delineating how a drug elicits nanostructural effects at the molecular, organelle and cellular levels. In conclusion, 3‐D EM techniques have entered a new era of structural biology and are poised to play a pivotal role in discovering new therapies targeting mitochondria for treating heart failure. Linked Articles This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc

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OPA1 in Cardiovascular Health and Disease

Cited by 16 publications

References 60 publications

Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

Mitochondrial-Shaping Proteins in Cardiac Health and Disease – the Long and the Short of It!

Three‐dimensional electron microscopy techniques for unravelling mitochondrial dysfunction in heart failure and identification of new pharmacological targets

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