Mitochondrial calcium uniporter regulator 1 (MCUR1)

Mitochondrial calcium uniporter regulator 1 (MCUR1) is a coiled-coil domain-containing protein embedded in the inner mitochondrial membrane. It functions primarily to regulate mitochondrial calcium uptake via direct interaction with the mitochondrial calcium uniporter (MCU) complex. MCUR1 sets the calcium threshold for mitochondrial permeability transition, modulating cell death and protecting cells against calcium overload injury during pathological conditions, such as ischemia and neurodegeneration. Recent research indicates it also contributes to oxidative phosphorylation and cellular bioenergetics, with MCUR1 deficiency linked to compromised ATP synthesis and activation of pro-survival autophagy. The exact mechanism of MCUR1 remains the subject of ongoing research, with conflicting reports describing additional roles in mitochondrial respiratory chain assembly or cytochrome c oxidase assembly. Its dysregulation has been associated with cardiovascular and neurodegenerative diseases, as well as inflammation and cancer. MCUR1 is considered a promising, though challenging, therapeutic target for diseases stemming from mitochondrial calcium dysregulation.

Other names

MCUR1C6orf79CCDC90AMCU regulator 1FLJ20958Coiled-coil domain-containing protein 90A, mitochondrialFMP32Epididymis secretory sperm binding protein

Inhibition or knockdown of MCUR1 raises calcium threshold for mitochondrial permeability transition pore opening, promoting cell survival under stress. Overexpression increases mitochondrial calcium uptake, leading to heightened reactive oxygen species and apoptotic susceptibility. Ruthenium derivatives (e.g., Ru360) can inhibit the effect of MCUR1 on calcium uptake indirectly.