Mitochondrial Ca²⁺ uptake was found to be mediated by the mitochondrial Ca²⁺ uniporter (MCU). MCU is a ruthenium‐red‐sensitive and highly selective Ca²⁺ ion channel that uptakes massive amount of Ca²⁺ across the inner membrane¹. MICU1 is a ~54 kDa. protein with an amino‐terminal mitochondrial targeting sequence, a predicted transmembrane helix, and a cytosolic C‐terminus containing two classical EF‐hand Ca²⁺‐binding domains².

Mitochondrial calcium uptake 1 (MICU1) protein was identified as an essential element of mitochondrial Ca²⁺ uptake. MCU initially takes up Ca²⁺ very rapidly, but when [Ca²⁺] inevitably increases inside the matrix, MICU1 binds Ca²⁺ through its EF‐hand domains, exerting an inhibitory role on MCU‐dependent Ca²⁺ entry³.

RNA expression of MICU1 is strongly correlated across a variety of tissues including: stomach, kidney, small and large intestine, cerebral cortex, cerebellum, hypothalamus, spinal cord and skeletal muscles⁴.

Loss-of-function mutations in MICU1 causes a brain and muscle disorder linked to primary alterations in mitochondrial Ca²⁺ signaling⁵.