A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca(2+) Transport in Diseases and Skeletal Muscle Function

The physical contact site between a mitochondrion and endoplasmic reticulum (ER), named the mitochondria-associated membrane (MAM), has emerged as a fundamental platform for regulating the functions of the two organelles and several cellular processes. This includes Ca(2+) transport from the ER to mitochondria, mitochondrial dynamics, autophagy, apoptosis signalling, ER stress signalling, redox reaction, and membrane structure maintenance. Consequently, the MAM is suggested to be involved in, and as a possible therapeutic target for, some common diseases and impairment in skeletal muscle function, such as insulin resistance and diabetes, obesity, neurodegenerative diseases, Duchenne muscular dystrophy, age-related muscle atrophy, and exercise-induced muscle damage. In the past decade, evidence suggests that alterations in Ca(2+) transport from the ER to mitochondria, mediated by the macromolecular complex formed by IP(3)R, Grp75, and VDAC1, may be a universal mechanism for how ER-mitochondria cross-talk is involved in different physiological/pathological conditions mentioned above. A better understanding of the ER (or sarcoplasmic reticulum in muscle)-mitochondria Ca(2+) transport system may provide a new perspective for exploring the mechanism of how the MAM is involved in the pathology of diseases and skeletal muscle dysfunction. This review provides a summary of recent research findings in this area.