Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+

TLDR

Mitochondria are essential for cellular energy metabolism, and their dysfunction is linked to many diseases; in cardiomyocytes, their close spatial arrangement with the sarcoplasmic reticulum enables Ca²⁺‑mediated crosstalk that influences cell survival and death pathways. This review aims to synthesize current knowledge on how the structural coupling between the sarcoplasmic reticulum and mitochondria affects cardiomyocyte function and death. We examine the structural basis of SR‑mitochondrial interactions and their functional consequences for Ca²⁺ signaling and cell fate in heart muscle cells.

Abstract

Mitochondria are key organelles in cell life whose dysfunction is associated with a variety of diseases. Their crucial role in intermediary metabolism and energy conversion makes them a preferred target in tissues, such as the heart, where the energetic demands are very high. In the cardiomyocyte, the spatial organization of mitochondria favors their interaction with the sarcoplasmic reticulum, thereby offering a mechanism for Ca(2+)-mediated crosstalk between these 2 organelles. Recently, the molecular basis for this interaction has begun to be unraveled, and we are learning how endoplasmic reticulum-mitochondrial interactions are often exploited by death signals, such as proapoptotic Bcl-2 family members, to amplify the cell death cascade. Here, we review our present understanding of the structural basis and the functional consequences of the close interaction between sarcoplasmic reticulum and mitochondria on cardiomyocyte function and death.