MPC1 Gene - Mitochondrial Pyruvate Carrier 1: Function, Mutations, and Disease

The MPC1 gene encodes the mitochondrial pyruvate carrier 1 protein, a subunit of the heterodimeric mitochondrial pyruvate carrier (MPC) complex. This complex is essential for the transport of pyruvate from the cytoplasm into the mitochondrial matrix, where it enters the tricarboxylic acid (TCA) cycle. MPC1 forms a functional complex with MPC2 to mediate pyruvate uptake, linking glycolysis to oxidative metabolism. Loss-of-function mutations in MPC1 cause mitochondrial pyruvate carrier deficiency, leading to lactic acidosis, developmental delay, and neurological impairment. Altered MPC1 expression is also implicated in cancer metabolism and metabolic disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Pyruvate metabolism (KEGG: hsa00620)

• Citrate cycle (TCA cycle) (KEGG: hsa00020)

• Metabolic pathways (KEGG: hsa01100)

• Mitochondrial pyruvate carrier (Reactome: R-HSA-8949613)

MPC1 is a 150-amino acid mitochondrial inner membrane protein that forms a heterodimeric complex with MPC2 to function as the mitochondrial pyruvate carrier. It contains two transmembrane domains and is essential for the import of pyruvate into the mitochondrial matrix. The protein is widely expressed, with highest levels in liver, heart, and kidney. Loss of MPC1 function disrupts the link between glycolysis and oxidative phosphorylation, leading to metabolic disorders and altered cancer cell metabolism.