Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988, PubMed:28615291, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:34463251, PubMed:36206740, PubMed:37036971, PubMed:37126688). MICU1 and MICU2 (or MICU3) form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:24560927, PubMed:26903221, PubMed:28615291, PubMed:32148862, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:36206740, PubMed:37036971, PubMed:37126688). At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:37036971, PubMed:37126688). At higher calcium levels, calcium-binding to MICU1 and MICU2 (or MICU3) induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU2 heterodimer away from the pore, allowing calcium permeation through the MCU channel (PubMed:32494073, PubMed:32667285, PubMed:32762847). Also required to protect against manganese toxicity by preventing manganese uptake by MCU: mechanistically, manganese- binding to its EF-hand domains does not induce any conformational change, maintaining MCU pore occlusion (PubMed:30082385, PubMed:30403999). Also acts as a barrier for inhibitors of the MCU channel, such as ruthenium red or its derivative Ru360 (PubMed:37244260). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:31427612, PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T- helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733). {ECO:0000269|PubMed:16002733, ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:22904319, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24313810, ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26341627, ECO:0000269|PubMed:26903221, ECO:0000269|PubMed:27099988, ECO:0000269|PubMed:28615291, ECO:0000269|PubMed:30082385, ECO:0000269|PubMed:30403999, ECO:0000269|PubMed:30454562, ECO:0000269|PubMed:30638448, ECO:0000269|PubMed:31427612, ECO:0000269|PubMed:32148862, ECO:0000269|PubMed:32494073, ECO:0000269|PubMed:32667285, ECO:0000269|PubMed:32762847, ECO:0000269|PubMed:32790952, ECO:0000269|PubMed:34463251, ECO:0000269|PubMed:36206740, ECO:0000269|PubMed:37036971, ECO:0000269|PubMed:37098122, ECO:0000269|PubMed:37126688, ECO:0000269|PubMed:37244260}. [Isoform 6]: Isoform that regulates mitochondrial calcium uniporter (MCU) in the skeletal muscle (By similarity). Compared to other isoforms, this isoform has higher affinity for calcium, promoting mitochondrial calcium uptake at lower calcium concentrations (By similarity). This allows a rapid response of mitochondrial metabolism and ensures sustained ATP production needed for resistance and strenuous exercise (By similarity). . This is the function of MICU1 (mitochondrial calcium uptake 1, ENSG00000107745).