MICU3

Tissue-specific calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which specifically regulates MCU channel activity in the central nervous system and skeletal muscle. Senses calcium level via its EF-hand domains: compared to MICU1 and MICU2, MICU3 has a higher affinity for calcium. MICU1 and MICU3 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium. At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake. At higher calcium levels, calcium-binding to MICU1 and MICU3 induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU3 heterodimer away from the pore, allowing calcium permeation through the MCU channel. The high calcium affinity of MICU3 lowers the calcium threshold necessary for calcium permeation through the MCU channel. The MICU1-MICU3 heterodimer promotes flexibility of neurotransmission in neuronal cells by enhancing mitochondrial calcium uptake in presynapses. It is also required to increase mitochondrial calcium uptake in skeletal muscle cells, thereby increasing ATP production (By similarity)..

Function from UniProtKB (Q86XE3), read 2026-09-23. CC BY 4.0.