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Mitochondrial dysfunction in pathophysiology of heart failure
Bo Zhou, Rong Tian
Bo Zhou, Rong Tian
Published August 20, 2018
Citation Information: J Clin Invest. 2018;128(9):3716-3726. https://doi.org/10.1172/JCI120849.
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Review Series

Mitochondrial dysfunction in pathophysiology of heart failure

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Abstract

Mitochondrial dysfunction has been implicated in the development of heart failure. Oxidative metabolism in mitochondria is the main energy source of the heart, and the inability to generate and transfer energy has long been considered the primary mechanism linking mitochondrial dysfunction and contractile failure. However, the role of mitochondria in heart failure is now increasingly recognized to be beyond that of a failed power plant. In this Review, we summarize recent evidence demonstrating vicious cycles of pathophysiological mechanisms during the pathological remodeling of the heart that drive mitochondrial contributions from being compensatory to being a suicide mission. These mechanisms include bottlenecks of metabolic flux, redox imbalance, protein modification, ROS-induced ROS generation, impaired mitochondrial Ca2+ homeostasis, and inflammation. The interpretation of these findings will lead us to novel avenues for disease mechanisms and therapy.

Authors

Bo Zhou, Rong Tian

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Figure 2

Mismatch of energy demand and generation drives the development of heart failure.

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Mismatch of energy demand and generation drives the development of heart...
In a healthy heart, energy production meets energy demand on a beat-by-beat basis. Pathological remodeling of the heart results in inefficiencies that increase energy demand but concomitantly reduce the capacity for energy supply. The subsequent metabolic remodeling in an attempt to regain energy homeostasis temporarily sustains the ATP level in the heart but likely drives the heart to failure via maladaptive circuits that produce mitochondrial stress. Current heart failure therapy aims at reducing the energy demand to alleviate the mismatch. Strategies that antagonize metabolic remodeling and/or mitochondrial stress signaling cascade could offer novel therapies. FAO, fatty acid oxidation.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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