Altered Mitochondrial Metabolism and Mechanosensation in the Failing Heart: Focus on Intracellular Calcium Signaling

Abstract

The heart consists of millions of cells, namely cardiomyocytes, which are highly organized in terms of structure and function, at both macroscale and microscale levels. Such meticulous organization is imperative for assuring the physiological pump-function of the heart. One of the key players for the electrical and mechanical synchronization and contraction is the calcium ion via the well-known calcium-induced calcium release process. In cardiovascular diseases, the structural organization is lost, resulting in morphological, electrical, and metabolic remodeling owing the imbalance of the calcium handling and promoting heart failure and arrhythmias. Recently, attention has been focused on the role of mitochondria, which seem to jeopardize these events by misbalancing the calcium processes. In this review, we highlight our recent findings, especially the role of mitochondria (dys)function in failing cardiomyocytes with respect to the calcium machinery.

Physical Activity and Redox Balance in the Elderly: Signal Transduction Mechanisms

“…In the heart, for example, Zima and Blatter [91] showed that the ROS produced during reperfusion of cardiac ischemic injury can affect ischemiarelated Ca(2+) overload. More recently, Cabassi and Miragoli [92] reviewed the important role of local environment (namely ROS and Ca 2+ ) in mitochondrial re-organization and fusion in failing cardiomyocytes. In particular, a correct interplay between Ca 2+ and ROS is important to avoid intracellular Ca 2+ increase during diastole that leads to cardiac arrhythmia [92].…”

Sport Performance and Manual Therapies: A Review on the Effects on Mitochondrial, Sarcoplasmatic and Ca2+ Flux Response

“…The usual methods used to apply mechanical stimuli to muscle cells in vivo or in vitro do not allow a thorough understanding of the observed phenomena, including the increase in strength after training or in flexibility after stretching exercises [ 30 ]. A deeper comprehension would be permitted by more sophisticated techniques such as tridimensional cytometry or scanning ion-conductance microscopy (SICM), which have the potential of assessing the mechanobiological behavior of muscle cells on nanometric size—that is, on mitochondrial size [ 29 , 30 , 36 ].…”

“…As reported in the scientific literature over the last years, changes in the cytoskeletal mechanical tension could affect mitochondria since these organelles and their ionic channels—the same channels that make Ca 2+ enter the mitochondrial matrix—are mechanosensitive structures [ 51 , 52 , 53 ]. In fact, due to changes in mechanical tension, the channels located in the mitochondrial membrane can open or close and, as a result, alter the cellular metabolism [ 36 , 51 , 52 , 53 ].…”

Mitochondrial mechanosensor in cardiovascular diseases

“…Furthermore, ROS and RNS are both protagonists in orchestrating calcium homeostasis within the cardiomyocytes (24); ROS are imperative in modulating the amplitude of calcium signals, while RNS have a role in modulating the calcium uptake in the SR via the SERCA2a protein (25). Much evidence has shown the relationship between Ca 2+ and ROS generation in mitochondria under physiological and pathological conditions (26).…”

“…Impairment of the structural interaction between mitochondria and the surrounding domain leads to cardiomyopathies. The sarcomere structure accommodates the subsarcolemmal mitochondrion underneath the crest ( 25 ) that directly interacts with the calcium-induced calcium release machinery, SERCA2 pump ( 58 ), and myofilaments of the Z-disc ( 59 ). Therefore, in failing cardiomyocytes, the sarcolemma integrity is lost ( Fig.…”