Mitochondrial Ca2+ uptake in skeletal muscle health and disease

TL;DR

This review discusses how mitochondrial calcium uptake influences skeletal muscle function and disease, highlighting its role in energy production, calcium signaling, and muscle degeneration.

Contribution

It provides a comprehensive overview of mitochondrial Ca2+ uptake mechanisms in skeletal muscle and their implications for health and disease.

Findings

Mitochondrial Ca2+ uptake promotes ATP production during muscle activity.

Excessive mitochondrial Ca2+ causes overload and cell dysfunction.

Mitochondrial Ca2+ dynamics are crucial for muscle excitation-contraction coupling.

Abstract

Muscle uses Ca2+ as a messenger to control contraction and relies on ATP to maintain the intracellular Ca2+ homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca2+ from their surroundings, a process called mitochondrial Ca2+ uptake. Under physiological conditions, Ca2+ uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca2+ overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca2+ uptake could shape spatio-temporal patterns of intracellular Ca2+ signaling. Malfunction of mitochondrial Ca2+ uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca2+ levels. Besides the sudden elevation of Ca2+ level induced by action potentials, Ca2+ transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca2+ uptake is fast and big enough to shape intracellular Ca2+ signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca2+ inside mitochondria. This review focuses on characterization of mitochondrial Ca2+ uptake in skeletal muscle and its role in muscle physiology and diseases.