Mechanism of MCUB-Dependent Inhibition of Mitochondrial Calcium Uptake.

ABSTRACT: Mitochondrial Ca²⁺ levels are regulated to balance stimulating respiration against the harm of Ca²⁺ overload. Contributing to this balance, the main channel transporting Ca²⁺ into the matrix, the mitochondrial Ca²⁺ uniporter, can incorporate a dominant-negative subunit (MCUB). MCUB is homologous to the pore-forming subunit MCU, but when present in the pore-lining tetramer, inhibits Ca²⁺ transport. Here, using cell lines deleted of both MCU and MCUB, we identify three factors that contribute to MCUB-dependent inhibition. First, MCUB protein requires MCU to express. The effect is mediated via the N-terminal domain (NTD) of MCUB. Replacement of the MCUB NTD with the MCU NTD recovers autonomous expression but fails to rescue Ca²⁺

SUBMITTER: Rai NK 

PROVIDER: S-EPMC11996009 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature