Evidence supporting the MICU1 occlusion mechanism and against the potentiation model in the mitochondrial calcium uniporter complex.

ABSTRACT: The mitochondrial calcium uniporter is a Ca²⁺ channel that imports cytoplasmic Ca²⁺ into the mitochondrial matrix to regulate cell bioenergetics, intracellular Ca²⁺ signaling, and apoptosis. The uniporter contains the pore-forming MCU subunit, an auxiliary EMRE protein, and the regulatory MICU1/MICU2 subunits. Structural and biochemical studies have suggested that MICU1 gates MCU by blocking/unblocking the pore. However, mitoplast patch-clamp experiments argue that MICU1 does not block, but instead potentiates MCU via allosteric mechanisms. Here, we address this direct clash of the proposed MICU1 function. Supporting the MICU1-occlusion mechanism, patch-clamp demonstrates that purified MICU1 strongly suppresses MCU Ca²⁺ currents, and this inhibit

SUBMITTER: Tsai CW 

PROVIDER: S-EPMC10120041 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature