Dysregulation of Mitochondrial Ca²⁺ Uptake and Sarcolemma Repair Underlie Muscle Weakness and Wasting in Patients and Mice Lacking MICU1.

ABSTRACT: Muscle function is regulated by Ca²⁺, which mediates excitation-contraction coupling, energy metabolism, adaptation to exercise, and sarcolemmal repair. Several of these actions rely on Ca²⁺ delivery to the mitochondrial matrix via the mitochondrial Ca²⁺ uniporter, the pore of which is formed by mitochondrial calcium uniporter (MCU). MCU's gatekeeping and cooperative activation are controlled by MICU1. Loss-of-protein mutation in MICU1 causes a neuromuscular disease. To determine the mechanisms underlying the muscle impairments, we used MICU1 patient cells and skeletal muscle-specific MICU1 knockout mice. Both these models show a lower threshold for MCU-mediated Ca²⁺ uptake. Lack of MICU1 is associated with impaired mitochondrial Ca²⁺

SUBMITTER: Debattisti V 

PROVIDER: S-EPMC7007691 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature