Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation.

ABSTRACT: Fibroblast to myofibroblast differentiation is crucial for the initial healing response but excessive myofibroblast activation leads to pathological fibrosis. Therefore, it is imperative to understand the mechanisms underlying myofibroblast formation. Here we report that mitochondrial calcium (_mCa²⁺) signaling is a regulatory mechanism in myofibroblast differentiation and fibrosis. We demonstrate that fibrotic signaling alters gating of the mitochondrial calcium uniporter (mtCU) in a MICU1-dependent fashion to reduce _mCa²⁺ uptake and induce coordinated changes in metabolism, i.e., increased glycolysis feeding anabolic pathways and glutaminolysis yielding increased α-ketoglutarate (αKG) bioavailability. _mCa²⁺-dependent metabo

SUBMITTER: Lombardi AA 

PROVIDER: S-EPMC6778142 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature