Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity.

ABSTRACT: The tricarboxylic acid (TCA) cycle converts the end products of glycolysis and fatty acid β-oxidation into the reducing equivalents NADH and FADH₂ Although mitochondrial matrix uptake of Ca²⁺ enhances ATP production, it remains unclear whether deprivation of mitochondrial TCA substrates alters mitochondrial Ca²⁺ flux. We investigated the effect of TCA cycle substrates on MCU-mediated mitochondrial matrix uptake of Ca²⁺, mitochondrial bioenergetics, and autophagic flux. Inhibition of glycolysis, mitochondrial pyruvate transport, or mitochondrial fatty acid transport triggered expression of the MCU gatekeeper MICU1 but not the MCU core subunit. Knockdown of mitochondrial pyruvate carrier (MPC) isoforms or expression of the dominant negative mutant

SUBMITTER: Nemani N 

PROVIDER: S-EPMC7667998 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature