Sarcoplasmic reticulum–mitochondria communication in cardiovascular pathophysiology

Abstract

Repetitive, calcium-mediated contractile activity renders cardiomyocytes critically dependent on a sustained energy supply and adequate calcium buffering, both of which are provided by mitochondria. Moreover, in vascular smooth muscle cells, mitochondrial metabolism modulates cell growth and proliferation, whereas cytosolic calcium levels regulate the arterial vascular tone. Physical and functional communication between mitochondria and sarco/endoplasmic reticulum and balanced mitochondrial dynamics seem to have a critical role for optimal calcium transfer to mitochondria, which is crucial in calcium homeostasis and mitochondrial metabolism in both types of muscle cells. Moreover, mitochondrial dysfunction has been associated with myocardial damage and dysregulation of vascular smooth muscle proliferation. Therefore, sarco/endoplasmic reticulum-mitochondria coupling and mitochondrial dynamics are now viewed as relevant factors in the pathogenesis of cardiac and vascular diseases, including coronary artery disease, heart failure, and pulmonary arterial hypertension. In this Review, we summarize the evidence related to the role of sarco/endoplasmic reticulum-mitochondria communication in cardiac and vascular muscle physiology, with a focus on how perturbations contribute to the pathogenesis of cardiovascular disorders.

Total Saponins of Aralia Elata (Miq) Seem Alleviate Calcium Homeostasis Imbalance and Endoplasmic Reticulum Stress-Related Apoptosis Induced by Myocardial Ischemia/Reperfusion Injury

“…In our study, LVEDP of the AS group tended to return to normal levels compared with the I/R group, which implied that AS could improve left ventricular diastolic function and increase myocardial positive inotropic effect [15,20]. In myocardial ischemia, mitochondrial oxidative phosphorylation and ATP production rapidly decreased, when Ca 2+ concentration in the mitochondrial matrix increased [29,30]. When the heart restored blood oxygen supply, a sufficient number of ROS generated, leading to cell membrane damage and permeability increase [29,31].…”

Mitochondrial Deformation During the Cardiac Mechanical Cycle

“…The consequences of mitochondrial deformation for structural cross‐talk with the SR are not known. Previously, cytoarchitectural perturbations have been shown to affect SR‐mitochondrial functional coupling (Wilding et al, ; Joubert et al, ; Lopez‐Crisosto et al, ). Additionally, we describe electron dense RyR‐like structures between T‐tubules and mitochondria.…”

“…The close proximity of the two compartments is thought to play a role in Ca 2+ signaling, exchange, and buffering and, consequently, to modulate excitation‐contraction coupling (Duchen et al, ; Rizzuto et al, ; Lu et al, ). SR‐mitochondrial Ca 2+ transfer is believed to occur through direct physical contact in cardiomyocytes (Lopez‐Crisosto et al, ), and the molecular identity of those tethers has been previously suggested as mitofusin (Naon et al, ). Some of the structures described here share structural similarity to mitochondrial ryanodine receptors, as proposed in earlier studies (Csordás et al, ; Franzini‐Armstrong, ; Lukyanenko et al, ).…”

New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

“…Indeed, alterations in these processes can lead to increase in cytosolic Ca 2+ with potential activation of detrimental pathways that have been associated with HF, including CaMKII (Zhang and Brown 2004). Additionally, alterations in SR-mitochondria contacts have been found in cardiac dysfunction and HF (Lopez-Crisosto et al 2017). …”