Meta-Biol

• Pathways

LETM1, which is located in the mitochondrial inner membrane (Tamai et al. 2008), exchanges two protons from the mitochondrial intermembrane space for a divalent calcium ion from the mitochondrial matrix (Tsai et al. 2014, Shao et al. 2016). LETM1 appears to participate in both calcium efflux and calcium influx (Doonan et al. 2014). Overexpression of LETM1, however, does not elevate calcium efflux from the mitochondrial matrix so the role of LETM1 in mitochondrial calcium flux is controversial (De Marchi et al. 2014). In human HeLa cells, knockdown of LETM1 causes an increase in mitochondrial calcium (Shao et al. 2016) however in mice, knockdown of Letm1 causes a reduction in mitochondrial calcium uptake and proton extrusion at low cytosolic calcium concentration (Jiang et al. 2013). LETM1 has also been proposed to act as a K+/H+ exchanger (Froschauer et al. 2005).