MICU proteins facilitate Ca²⁺-dependent mitochondrial metabolon formation to regulate cellular energetics - independent of MCU.

ABSTRACT: Mitochondrial matrix Ca²⁺ concentration ([_matrixCa²⁺]) is theorized to be an essential regulator of mitochondrial metabolism by positively regulating key mitochondrial dehydrogenases. However, ablation or functional inhibition of the mitochondrial calcium uniporter channel (mtCU) fails to significantly perturb basal metabolism and is largely phenotypically silent in the absence of stress. This begs the question, what are the primary molecular mechanisms regulating calcium-dependent changes in metabolism? The primary function of MICU proteins (MICU1, MICU2, and MICU3) is reported to be gatekeeping of the mtCU and regulating mitochondrial Ca²⁺ uptake. Here, we demonstrate that MICU proteins function in coordination to impart Ca^2+-depende

SUBMITTER: Cohen HM 

PROVIDER: S-EPMC12270237 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature