Blockade of MCU-Mediated Ca²⁺ Uptake Perturbs Lipid Metabolism via PP4-Dependent AMPK Dephosphorylation.

ABSTRACT: Mitochondrial Ca²⁺ uniporter (MCU)-mediated Ca²⁺ uptake promotes the buildup of reducing equivalents that fuel oxidative phosphorylation for cellular metabolism. Although MCU modulates mitochondrial bioenergetics, its function in energy homeostasis in vivo remains elusive. Here we demonstrate that deletion of the Mcu gene in mouse liver (MCU^Δhep) and in Danio rerio by CRISPR/Cas9 inhibits mitochondrial Ca²⁺ (_mCa²⁺) uptake, delays cytosolic Ca²⁺ (_cCa²⁺) clearance, reduces oxidative phosphorylation, and leads to increased lipid accumulation. Elevated hepatic lipids in MCU^Δhep were a direct result of extramitochondrial Ca²⁺-dependent protein phosphatase-4 (PP4) activity, wh

SUBMITTER: Tomar D 

PROVIDER: S-EPMC6512325 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature