Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal Syndrome

Sumida, Maki; Doi, Kent; Ogasawara, Emi; Yamashita, Tetsushi; Hamasaki, Yoshifumi; Kariya, Taro; Takimoto, Eiki; Yahagi, Naoki; Nangaku, Masaomi; Noiri, Eisei

doi:10.1681/asn.2014080750

Cited by 96 publications

(100 citation statements)

References 44 publications

(46 reference statements)

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“…Indeed, hydroxylamine derivatives, which activate optic atrophy-1 and promote the fusion of inner mitochondrial membranes, ameliorated lung damage in a murine model of pulmonary arterial hypertension [51]. Recently, treatment with a drug that prevents activation of the mitochondrial fission marker dynamin related protein (DRP)-1 ameliorated vascular remodeling and inflammation in spontaneously hypertensive rats [52], in accordance with previous observations in cardiomyocytes subjected to renal [53] and cardiac [54] reperfusion injury.…”

Section: Mechanisms Of Mitoprotectionsupporting

confidence: 75%

Enhancing Mitochondrial Health to Treat Hypertension

Eirin

Lerman

2018

Curr Hypertens Rep

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Purpose of the Review: This review summarizes literature pertaining to the dawning field of therapeutic targeting of mitochondria in hypertension, and discusses the potential of these interventions to ameliorate hypertension-induced organ damage. Recent Findings: In recent years, mitochondrial dysfunction has been reported as an important contributor to the pathogenesis of hypertension-related renal, cardiac, and vascular disease. This in turn prompted development of novel mitochondria-targeted compounds, some of which have shown promising efficacy in experimental studies and safety in clinical trials. In addition, drugs that do not directly target mitochondria have shown remarkable benefits in preserving these organelles in experimental hypertension. Summary: Enhancing mitochondrial health is emerging as a novel feasible approach to treat hypertension. Future perspectives include mechanistic experimental studies to establish a cause-effect relationship between mitochondrial dysfunction and hypertension and further clinical trials to confirm the reno-, cardio-, and vasculo-protective properties of these compounds in hypertension.

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Section: Mechanisms Of Mitoprotectionsupporting

confidence: 75%

Enhancing Mitochondrial Health to Treat Hypertension

Eirin

Lerman

2018

Curr Hypertens Rep

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“…Manipulation of mitochondrial dynamics is a new strategy to decrease cardiac injury during ischemia-reperfusion. 197, 198 Thus, the enhanced oxidant production present in the aged heart may impair protective mitochondria fission-based responses to superimposed disease. Modulation of mitochondrial dynamic changes may be a strategy to attenuate the deleterious impact of age-related defects in the ETC.…”

Section: Mitochondrial Fission and Fusionmentioning

confidence: 99%

Mitochondrial Metabolism in Aging Heart

Lesnefsky

Chen

Hoppel

2016

Circulation Research

260

207

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Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction.

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“…Another interesting example is the work by Sumida et al [229] where they showed that mouse kidney subjected to acute IRI induced mitochondrial fragmentation in the heart, resulting in apoptosis and cardiac dysfunction, the effects of which could be reverse by pharmacological inhibition of Drp1 using mdivi-1 .…”

Section: Mitochondrial Fusion and Fission Proteins In Cardiac Healthmentioning

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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Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal Syndrome

Cited by 96 publications

References 44 publications

Enhancing Mitochondrial Health to Treat Hypertension

Enhancing Mitochondrial Health to Treat Hypertension

Mitochondrial Metabolism in Aging Heart

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

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