SLC25A23 augments mitochondrial Ca2+ uptake, interacts with MCU, and induces oxidative stress–mediated cell death

摘要: Emerging findings suggest that two lineages of mitochondrial Ca2+ uptake participate during active and resting states: 1) the major eukaryotic membrane potential–dependent uniporter 2) evolutionarily conserved exchangers solute carriers, which are also involved in ion transport. Although influx across inner maintains metabolic functions cell death signal transduction, mechanisms regulate accumulation unclear. Solute carriers—solute carrier 25A23 (SLC25A23), SLC25A24, SLC25A25—represent a family EF-hand–containing proteins transport Mg-ATP/Pi membrane. RNA interference–mediated knockdown SLC25A23 but not SLC25A24 SLC25A25 decreases reduces cytosolic clearance after histamine stimulation. Ectopic expression EF-hand–domain mutants exhibits dominant-negative phenotype reduced uptake. In addition, interacts with (MCU; CCDC109A) MICU1 (CBARA1) while increasing IMCU. lowers basal mROS accumulation, attenuates oxidant-induced ATP decline, death. Further, reconstitution short hairpin RNA–insensitive cDNA restores superoxide production. These indicate plays an important role matrix influx.