Mechanisms of dual modulatory effects of spermine on the mitochondrial calcium uniporter complex.

ABSTRACT: The mitochondrial Ca2+ uniporter mediates the crucial cellular process of mitochondrial Ca2+ uptake, which regulates cell bioenergetics, intracellular Ca2+ signaling, and cell death initiation. The uniporter contains the pore-forming MCU subunit, an EMRE protein that binds to MCU, and the regulatory MICU1 subunit, which can dimerize with MICU1 or MICU2 and under resting cellular [Ca2+] occludes the MCU pore. It has been known for decades that spermine, which is ubiquitously present in animal cells, can enhance mitochondrial Ca2+ uptake, but the underlying mechanisms remain unclear. Here, we show that spermine exerts dual modulatory effects on the uniporter. In physiological concentrations of spermine, it enhances uniporter activity by breaking the physical interactions between MCU and the

SUBMITTER: Tu YC 

PROVIDER: S-EPMC10274775 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature