MICU1 and MICU2 control mitochondrial calcium signaling in the mammalian heart.

ABSTRACT: Activating Ca²⁺-sensitive enzymes of oxidative metabolism while preventing calcium overload that leads to mitochondrial and cellular injury requires dynamic control of mitochondrial Ca²⁺ uptake. This is ensured by the mitochondrial calcium uptake (MICU)1/2 proteins that gate the pore of the mitochondrial calcium uniporter (mtCU). MICU1 is relatively sparse in the heart, and recent studies claimed the mammalian heart lacks MICU1 gating of mtCU. However, genetic models have not been tested. We find that MICU1 is present in a complex with MCU in nonfailing human hearts. Furthermore, using murine genetic models and pharmacology, we show that MICU1 and MICU2 control cardiac mitochondrial Ca²⁺ influx, and that MICU1 deletion alters cardiomyocyte mitochondrial cal

SUBMITTER: Hasan P 

PROVIDER: S-EPMC11363308 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature