Breaking the link between sarcoplasmic reticulum calcium leakage and mitochondria to counteract unloading-induced muscle atrophy.

Abstract

In muscle fibers, unloading and disuse cause an increase in resting calcium concentrations in the cytosol and mitochondrial matrix. S107, a stabilizer of the Ryanodine Receptor calcium channel (RyR), blocks the leakage from the sarcoplasmic reticulum and lowers mitochondrial calcium concentrations without altering cytosolic calcium levels, as demonstrated in a recent article published in Pflugers Archives (Sidorenko et al. 2025). This finding is important as it shows that, even at rest, calcium entry into the mitochondria is influenced by RyR leakage, thanks to the mitochondria unique location near the sarcoplasmic reticulum membranes. Given the role of mitochondrial function in controlling muscle fiber size, these findings may have a significant translational relevance in the treatment of disuse-induced atrophy.