8.A.44.1.1
The mitochondrial EF hand Ca²⁺ uptake porter (MCU; TC# 1.A.77) regulator (MICU1; 476 aas) (also called Ca²⁺-binding atopy-related autoantigen CALC, or AraCALC) (Perocchi et al., 2010). It is homologous to the bifunctional glutamine amidotransferase/anthranylate phosphoribosyl transferase (PRK14607).  It contributes to metabolism-insulin secretion coupling in clonal pancreatic beta-cells (Alam et al. 2012). MCU forms a complex with MICU1, MICU2 and EMRE in animals (Yuan et al. 2020). Human duchenne muscular dystrophy is associated with the inhibition of calcium uniport in mitochondria and an increased sensitivity of the organelles to the calcium-induced permeability transition (Dubinin et al. 2020). Cardiac mitochondria exhibit higher calcium retention capacity and higher rates of calcium uptake during sleep periods. This is associated with higher expression of clock gene Bmal1, lower expression of per2, greater expression of MICU1 gene (mitochondrial calcium uptake 1), and lower expression of the mitochondrial transition pore regulator gene cyclophilin D. Protein levels of mitochondrial calcium uniporter (MCU), MICU2, and sodium/calcium exchanger (NCLX) were also higher at sleep onset relative to wake periods. While complex I and II-dependent oxygen utilization and the transmembrane potential of cardiac mitochondria were lower during sleep, ROS production was increased, presumably due to mitochondrial calcium sequestration. Thus, retaining mitochondrial calcium in the heart during sleep dissipates the membrane potential, slows respiratory activities, and increases ROS levels, which may contribute to increased vulnerability to cardiac stress during the sleep-wake transition. This pronounced daily oscillations in mitochondrial functions pertaining to stress vulnerability may at least in part explain diurnal prevalence of cardiac pathologies.