Loss of mitochondrial Ca²⁺ uptake protein 3 impairs skeletal muscle calcium handling and exercise capacity.

ABSTRACT: Mitochondrial calcium concentration ([Ca²⁺ ]_m ) plays an essential role in bioenergetics, and loss of [Ca²⁺ ]_m homeostasis can trigger diseases and cell death in numerous cell types. Ca²⁺ uptake into mitochondria occurs via the mitochondrial Ca²⁺ uniporter (MCU), which is regulated by three mitochondrial Ca²⁺ uptake (MICU) proteins localized in the intermembrane space, MICU1, 2, and 3. We generated a mouse model of systemic MICU3 ablation and examined its physiological role in skeletal muscle. We found that loss of MICU3 led to impaired exercise capacity. When the muscles were directly stimulated there was a decrease in time to fatigue. MICU3 ablation significantly increased the maximal force of the KO muscle and

SUBMITTER: Roman B 

PROVIDER: S-EPMC10824360 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature