Mitochondrial Dynamism and Cardiac Fate

Dorn, Gerald W.

doi:10.1253/circj.cj-13-0453

Cited by 27 publications

(24 citation statements)

References 99 publications

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“…15 We showed that both agents opened mPTP and depolarized mitochondrial membrane potential (∆Ψm), indicating a functional link between MT reorganization and mPTP in cardiac Mitochondria undergo frequent and dynamic morphological changes, and this is regulated by fission and fusion proteins located in the IMM and OMM. 12 According to recent reports, among these, mitofusin-2 (Mfn2), a fusion protein existing in the OMM, is related to the regulation of mPTP. 13 Because both Mfn2 and the Miro-Milton-KHC complex are located in the OMM, interaction could occur between these proteins.…”

Section: Microtubules and Mptpmentioning

confidence: 99%

“…The mitochondrial fusion is regulated by Mfn2 located on the OMM and optic atrophy 1 (Opa1) located on the IMM. 12 In the neuron system, Mfn2 directly interacts with Miro, and both Mfn2 and Miro are required to cooperatively mediate mitochondrial transport. 21 Miro can regulate mitochondrial morphology, independently from mitochondrial transport in H9c2 cells.…”

Section: Mt Disorganization Induces Mitochondrial Fragmentation In H9mentioning

confidence: 99%

“…It is known that mitochondrial fragmentation is also related to ROS production. 12 Thus, synergistic effects on the generation of ROS by mPTP and mitochondrial fragmentation could lead to positive feedback about mPTP opening. In contrast, structural destruction than ROS may have a larger impact on nocodazole-induced mPTP opening.…”

Section: Stabilization Of Mts and Mptpmentioning

confidence: 99%

See 2 more Smart Citations

Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes

Kumazawa

Katoh

Nonaka

et al. 2014

Circ J

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Section: Microtubules and Mptpmentioning

confidence: 99%

Section: Mt Disorganization Induces Mitochondrial Fragmentation In H9mentioning

confidence: 99%

Section: Stabilization Of Mts and Mptpmentioning

confidence: 99%

See 1 more Smart Citation

Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes

Kumazawa

Katoh

Nonaka

et al. 2014

Circ J

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“…9 Mitochondria also generate ROS as natural byproducts of oxygen metabolism in the electron transport chain. Under normal conditions, most of the electrochemical proton gradient is used to generate ATP through ATP synthase, and only 0.1% of the total oxygen consumption leaks from the respiratory chain to generate ROS.…”

Section: Mitochondrial Ros Production In Dmmentioning

confidence: 99%

Production of Reactive Oxygen Species in the Diabetic Heart

Teshima

Takahashi

Nishio

et al. 2014

Circ J

116

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300TESHIMA Y et al. Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp iabetes mellitus (DM) is an independent risk factor of heart failure. The Framingham Heart Study reported that the frequency of heart failure is 2-fold higher in male diabetics and 5-fold higher in female diabetics than in age-matched control subjects. 1 An increase in reactive oxygen species (ROS) has been regarded as a dominant mechanism of cardiac dysfunction in patients with DM. 2-4 ROS are important intracellular signaling molecules and mediate various cellular functions, including activation of transcriptional factors, protein kinases, and ion channels; however, high levels of ROS are detrimental to cardiomyocytes. In physiological conditions, ROS levels are appropriately controlled by endogenous antioxidant systems to minimize oxidative cellular damage. Oxidative stress occurs when ROS production overwhelms antioxidant capacity in pathological conditions. It is apparent that ROS production and oxidative stress are increased in the diabetic heart, and oxidative stress induces various cardiovascular complications, including cardiac dysfunction, which is facilitated by inflammation, apoptosis, and fibrosis (Figure 1). [5][6][7][8] There is accumulating evidence that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play a pivotal role in ROS production in the diabetic heart. In this review, we will summarize the mechanisms of ROS increase in the diabetic heart focusing on the roles of mitochondria and NADPH oxidase. Mitochondria Mitochondrial ROS Production in DMMitochondria not only provide energy, but also provoke apoptosis, which is regulated by mitochondrial dynamics. 9 Mitochondria also generate ROS as natural byproducts of oxygen metabolism in the electron transport chain. Under normal conditions, most of the electrochemical proton gradient is used to generate ATP through ATP synthase, and only 0.1% of the total oxygen consumption leaks from the respiratory chain to generate ROS. However, a high intracellular glucose concentration increases the flux of electron transfer donors (NADH and FADH2) into the mitochondrial respiratory chain by oxidizing glucose-derived pyruvate. The resulting hyperpolarization of the mitochondrial inner membrane potential partially inhibits electron transport in complex III and accumulates electrons to ubisemiquinone to generate superoxide. 10,11 Therefore, mitochondrial respiration is the principal source of ROS in Reactive oxygen species (ROS) are the main facilitators of cardiovascular complications in diabetes mellitus (DM), and the ROS level is increased in cultured cells exposed to high glucose concentrations or in diabetic animal models. Emerging evidence shows that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are dominant mechanisms of ROS production in the diabetic heart. Hyperpolarization of the mitochondrial inner membrane potentials and impaired mitochondrial function promote ROS production ...

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“…Morphology is regulated by mitochondrial fusion (MFN1, MFN2, OPA1) and fission (DRP1, FIS1) proteins. 5,6 Mitochondrial fission has been shown to precede mitophagy, and mitochondrial elongation during starvation prevents mitochondrial destruction by mitophagy (Figure 1). 4,7 BCL-2 and BCL-XL are anti-apoptotic proteins that bind BECLIN-1 to prevent its activation, and disruption of this interaction is essential for initiation of autophagy.…”

Section: Multiple Pathways Regulate Myocardial Mitophagymentioning

confidence: 99%

Mitochondrial Autophagy

Thomas

Gustafsson

2013

Circ J

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Efficient and functional mitochondrial networks are essential for myocardial contraction and cardiomyocyte survival. Mitochondrial autophagy (mitophagy) refers to selective sequestration of mitochondria by autophagosomes, which subsequently deliver them to lysosomes for destruction. This process is essential for myocardial homeostasis and adaptation to stress. Elimination of damaged mitochondria protects against cell death, as well as stimulates mitochondrial biogenesis. Mitophagy is a tightly controlled and highly selective process. It is modulated by mitochondrial fission and fusion proteins, BCL-2 family proteins, and the PINK1/Parkin pathway. Recent studies have provided evidence that miRNAs can regulate mitophagy by controlling the expression of essential proteins involved in the process. Disruption of autophagy leads to rapid accumulation of dysfunctional mitochondria, and diseases associated with impaired autophagy produce severe cardiomyopathies. Thus, autophagy and mitophagy pathways hold promise as new therapeutic targets for clinical cardiac care.

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Mitochondrial Dynamism and Cardiac Fate

Cited by 27 publications

References 99 publications

Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes

Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes

Production of Reactive Oxygen Species in the Diabetic Heart

Mitochondrial Autophagy

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