A controversial issue: Can mitochondria modulate cytosolic calcium and contraction of skeletal muscle fibers? (vol 154, e202213167, 2022)

Mitochondria are characterized by a high capacity to accumulate calcium thanks to the electrochemical gradient created by the extrusion of protons in the respiratory chain. Thereby calcium can enter crossing the inner mitochondrial membrane via MCU complex, a high-capacity, low-affinity transport mechanism. Calcium uptake serves numerous purposes, among them the regulation of three dehydrogenases of the citric cycle, apoptosis via permeability transition, and, in some cell types, modulation of cytosolic calcium transients. This Review is focused on mitochondrial calcium uptake in skeletal muscle fibers and aims to reanalyze its functional impact. In particular, we ask whether mitochondrial calcium uptake is relevant for the control of cytosolic calcium transients and therefore of contractile performance. Recent data suggest that this may be the case, at least in particular conditions, as modified expression of MCU complex subunits or of proteins involved in mitochondrial dynamics and ablation of the main cytosolic calcium buffer, parvalbumin. In skeletal muscle fibers, mitochondria calcium uptake is relevant for metabolic activation, trophic regulation, and apoptosis. It is still debated whether mitochondria can modulate cytosolic calcium transients and contractile performance. Here, we discuss evidence in favor or against this possibility.