Meta-Biol

• Pathways

The mitochondrial calcium uniporter (MCU) is a protein complex located in the mitochondrial inner membrane that transports divalent calcium ions (Ca2+) from the mitochondrial intermembrane space, across the mitochondrial inner membrane, and into the mitochondrial matrix (De Stefani et al. 2011, Baughman et al. 2011, Chaudhuri et al. 2013) where the Ca2+ allosterically regulates matrix enzymes such as pyruvate dehydrogenase, isocitrate dehydrogenase, and the 2-oxoglutarate dehydrogenase complex (Denton and McCormack 1980). The MCU subunit of the complex forms the actual pore in the inner membrane and is suggested to interact with VDAC1 (Liao et al. 2015). MCUB is a differentially expressed paralog of MCU that is likewise located in the inner membrane but acts as an inhibitor of calcium import (Raffaello et al. 2013). MICU1 and MICU2 (or MICU3 in neurons) regulate the pore so that it opens only when cellular calcium concentrations are high (Perocchi et al. 2010, Plovanich et al. 2013, Patron et al. 2014, Kamer and Mootha et al. 2014). The SMDT1 (EMRE) subunit forms part of the pore and binds MICU1 and MICU2 (Sancak et al. 2013, Tsai et al. 2016). MCUR1 appears to associate with MCU, but its function is uncertain (Paupe et al. 2015, Chaudhuri et al. 2016). Other calcium channels are also detected in the mitochondrial inner membrane (Bondarenko et al. 2014).