Mitochondrial calcium uniporter (MCU) is a 480 kDa mitochondrial inner membrane protein, a multimer that forms a calcium (Ca²⁺) channel in the lipid bilayer. MCU is one of the most important and highly selective channels responsible for mitochondrial calcium uptake. This uptake plays an important role in cell energy balance and in cell fate determination.

The MCU protein is comprised of Mcu which functions as the pore-forming and calcium-conducting subunit, encoded by the Ccdc109a gene. The other units- MICU1 (calcium uptake protein 1, mitochondrial), MICU2 (calcium uptake protein 2, mitochondrial), EMRE (essential MCU regulator, mitochondrial), MCUR1 (mitochondrial calcium uniporter regulator 1) and MCUb (calcium uniporter regulatory subunit MCUb, mitochondrial) all function as regulatory subunits^1-3.

Studies have demonstrated that knockdown of Mcu uniport in isolated cardiomyocytes enhances peak levels in cytosolic Ca²⁺ oscillation, resulting in an increase of muscle contraction².

Mcu pore-forming subunit is a homo-oligomer with two coil-coiled domains and two transmembrane domains (TM) separated by a short hydrophilic loop enriched in acidic amino acids. The second transmembrane helices from five Mcu subunits form a hydrophilic pore in the inner membrane of the mitochondria. The DXXE motif forms the pore entrance in the inter-membrane space. The N- and the C-terminus of MCU face the matrix^1,3.