Abstract
Abnormal mitochondrial morphology, especially fragmented mitochondria, and mitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway regulates mitochondrial morphology and function under pathophysiological conditions such as HF. Mitochondria change their shape and location via the activity of mitochondrial fission and fusion proteins. This mechanism is suggested as an important modulator for mitochondrial and cellular functions including bioenergetics, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca2+ signaling, cell growth, and death in the mammalian cell- and tissue-specific manners. Recent reports show that a mitochondrial fission protein, dynamin-like/related protein 1 (DLP1/Drp1), is post-translationally modified via cell signaling pathways, which control its subcellular localization, stability, and activity in cardiomyocytes/heart. In this review, we summarize the possible molecular mechanisms for causing post-translational modifications (PTMs) of DLP1/Drp1 in cardiomyocytes, and further discuss how these PTMs of DLP1/Drp1 mediate abnormal mitochondrial morphology and mitochondrial dysfunction under adrenergic signaling activation that contributes to the development and progression of HF.
Highlights
Mitochondria are essential eukaryotic organelles that generate the energy necessary for a myriad of cellular processes
In the heart, cardiac mitochondria occupy over 30% of the cell volume [6,26] and are usually classified into three groups according to their location: intermyofibrillar mitochondria (IFM), subsarcolemmal mitochondria (SSM) and perinuclear mitochondria (PNM) [7,15]
Though it is still unclear whether the alteration in the stoichiometric ratio of fission/fusion proteins creates an imbalance between fusion and fission in heart failure (HF) ([34,35,85]), these observations have introduced the idea that post-translational modifications (PTMs) of mitochondrial fission/fusion proteins by AR
Summary
Mitochondria are essential eukaryotic organelles that generate the energy necessary for a myriad of cellular processes (see reviews [1,2,3,4,5]). Since the experimental techniques for detecting mitochondrial fission events in live myofibrils are still being developed [25], the frequency and speed of fission events in striated muscles including adult CMs remain unclear It is largely unknown whether mitochondrial fission/fusion events influence the beat-to-beat-based regulation of excitation–contraction (E–C) coupling in CMs. In the heart (especially in the ventricles), cardiac mitochondria occupy over 30% of the cell volume [6,26] and are usually classified into three groups according to their location: intermyofibrillar mitochondria (IFM), subsarcolemmal mitochondria (SSM) and perinuclear mitochondria (PNM) [7,15].
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