Proteolytic control of the mitochondrial calcium uniporter complex.

ABSTRACT: The mitochondrial calcium uniporter is a Ca²⁺-activated Ca²⁺ channel complex mediating mitochondrial Ca²⁺ uptake, a process crucial for Ca²⁺ signaling, bioenergetics, and cell death. The uniporter is composed of the pore-forming MCU protein, the gatekeeping MICU1 and MICU2 subunits, and EMRE, a single-pass membrane protein that links MCU and MICU1 together. As a bridging subunit required for channel function, EMRE could paradoxically inhibit uniporter complex formation if expressed in excess. Here, we show that mitochondrial mAAA proteases AFG3L2 and SPG7 rapidly degrade unassembled EMRE using the energy of ATP hydrolysis. Once EMRE is incorporated into the complex, its turnover is inhibited >15-fold. Protease-resistant EMRE mutants produce unipo

SUBMITTER: Tsai CW 

PROVIDER: S-EPMC5410796 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature