The Mitochondrial Ca²⁺ uniporter is a central regulator of interorganellar Ca²⁺ transfer and NFAT activation.

ABSTRACT: Mitochondrial Ca²⁺ uptake tailors the strength of stimulation of plasma membrane phospholipase C-coupled receptors to that of cellular bioenergetics. However, how Ca²⁺ uptake by the mitochondrial Ca²⁺ uniporter (MCU) shapes receptor-evoked interorganellar Ca²⁺ signaling is unknown. Here, we used CRISPR/Cas9 gene knockout, subcellular Ca²⁺ imaging, and mathematical modeling to show that MCU is a universal regulator of intracellular Ca²⁺ signaling across mammalian cell types. MCU activity sustains cytosolic Ca²⁺ signaling by preventing Ca²⁺-dependent inactivation of store-operated Ca²⁺ release-activated Ca²⁺ channels and by inhibiting Ca²⁺ extrusion. Paradoxically, MCU kno

SUBMITTER: Yoast RE 

PROVIDER: S-EPMC8496184 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature