The mitochondrial calcium uniporter is a multi-subunit Ca2+-activated Ca2+ channel, made up of the pore-forming the mitochondrial calcium uniporter (MCU) protein, a metazoan-specific EMRE subunit, and MICU1/MICU2, which mediate Ca2+ activation[2]. Ca2+ uptake by mitochondria regulates bioenergetics, apoptosis, and Ca2+ signaling. The primary pathway for mitochondrial Ca2+ uptake is the MCU, a Ca2+ selective ion channel in the inner mitochondrial membrane[3]. MCU dysfunction has been shown to alter mitochondrial Ca2+ dynamics, in turn eliciting cell apoptosis. Changes in mitochondrial Ca2+ uptake have been implicated in pathological conditions affecting multiple organs, including the heart, skeletal muscle, and brain[4]. MCU, Nrf2, and MICU1 were strongly expressed in OSCC as compared to normal tissues, while MICU2 was relatively weakly expressed in OSCC tissues. Knockdown of MCU distinctly weakened proliferation and migration and lowered MMP level in CAL 27 cells[5]. MCU had a higher expression in gastric cancer tissues than normal tissues. Compared to gastric cancer tissues, its expression was significantly higher after omental metastasis. MCU expression was significantly correlated with depth of invasion (p=0.048), lymph metastasis (p=0.027), TNM stage (p=0.036) and distant metastasis (p=0.029)[6]. MCU-i4 is a novel negative modulator of the MCU, binding MICU1 and impairing muscle cell growth[7].
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