Mitochondrial calcium uniporter complex (MCU complex) (MCU complex)

The Mitochondrial calcium uniporter (MCU) complex is a multi-protein assembly located in the inner mitochondrial membrane that mediates the highly selective uptake of calcium ions (Ca2+) from the cytosol into the mitochondrial matrix (PubMed: 21685886). It consists of the pore-forming subunit MCU, the essential regulator EMRE, and regulatory subunits MICU1 and MICU2 which act as gatekeepers to prevent calcium overload at low cytosolic concentrations (PubMed: 23101630). This complex plays a critical role in cellular metabolism by activating Ca2+-dependent enzymes in the Krebs cycle, thereby matching ATP production with energy demand (PubMed: 24113413). Dysregulation of mitochondrial Ca2+ handling is a hallmark of several diseases; for instance, Ca2+ overload can trigger the opening of the mitochondrial permeability transition pore (mPTP), leading to cell death in ischemia-reperfusion injury and neurodegeneration (PubMed: 29033138). Conversely, reduced MCU activity is observed in certain cancers to avoid apoptosis and promote glycolytic metabolism (PubMed: 24631452). Pharmacological modulators, including inhibitors like Ru360 and DS16570511 or activators like Kaempferol, are being investigated for their potential to treat cardiovascular and metabolic disorders (PubMed: 30635517).

Other names

Mitochondrial calcium uniporterMCUMitochondrial Ca2+ uniporterMitochondrial calcium handling machineryCCDC109AMitochondrial calcium uniporter holocomplex

Modulation of the mitochondrial calcium uniporter pore activity or its regulatory gatekeeping mechanisms to control mitochondrial calcium influx.