MPC1:MPC2 imports PYR, H+ to mitochondrial matrix

Stable Identifier
Reaction [transition]
Homo sapiens
MPC1:MPC2 cotransports PYR, H+ from cytosol to mitochondrial matrix, PYR + H+ (cytosol) => PYR + H+ (mitochondrial matrix)
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Pyruvate (PYR) and a proton (H+) are cotransported from the mitochondrial intermembrane space to the mitochondrial matrix, mediated by a complex of mitochondrial pyruvate carriers located in the inner mitochondrial membrane. The complex is a heterodimer of MPC2 with either MCP1 or, in testis, MPC1L (Bricker et al., 2012; McCommis & Finck, 2015; Vanderperre et al., 2016; Lee et al., 2020; reviewed in Quesñay et al., 2020). However, the viability of an MPC2 oligomer has been shown, as well (Nagampalli et al., 2018). The proton gradient across the inner mitochondrial membrane must be maintained for ATP production. Transport of PYR across this membrane would collapse this gradient; therefore, PYR is cotransported with H+. Studies of pyruvate uptake in rats indicate that it is specific, saturable, and competitively inhibitable, indicating a specific role for a membrane transport protein (Papa et al. 1971, Halestrap & Denton 1974), and the stoichiometry of the human reaction is inferred from this work. Mutations in MPC1 or MPC2 can lead to mitochondrial pyruvate carrier deficiency (MPYCD, MIM:614741; Bricker et al., 2012; Pujol et al., 2023).
Literature References
PubMed ID Title Journal Year
29472561 Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter

de Oliveira, JF, Fala, AM, Quesñay, JEN, Islam, Z, Silva, ACT, Birch, J, Ascenção, CFR, Dias, SMG, Nagampalli, RSK, Pauletti, BA, Sebinelli, HG, Ciancaglini, P, Ambrosio, ALB, Consonni, SR, Leme, AFP, Girard, RMBM, Franchini, KG, Silber, AM, Moraes, I, Adamoski, D

Sci Rep 2018
36417180 MPC2 variants disrupt mitochondrial pyruvate metabolism and cause an early-onset mitochondriopathy

Boutron, A, Slama, A, Youssef-Turki, IB, Dard, R, Kraoua, I, Bault, JP, Wai, T, Omar, S, Pujol, C, Gaignard, P, Lebigot, E, Galai, S

Brain 2023
4822737 Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate

Denton, RM, Halestrap, AP

Biochem. J. 1974
25748677 Mitochondrial pyruvate transport: a historical perspective and future research directions

Finck, BN, McCommis, KS

Biochem. J. 2015
33227948 Insights on the Quest for the Structure-Function Relationship of the Mitochondrial Pyruvate Carrier

Ambrosio, ALB, Quesñay, JEN, Balakrishnan, V, Dias, SMG, Nagampalli, RSK, Dafforn, TR, Moraes, I, Pollock, NL, Lee, SC

Biology (Basel) 2020
11945601 The transport of pyruvate in rat liver mitochondria

Meduri, B, Paradies, G, Papa, S, Francavilla, A

FEBS Lett 1971
27317664 MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells

Cermakova, K, Escoffier, J, Bender, T, Vanderperre, B, Nef, S, Martinou, JC, Kaba, M

J Biol Chem 2016
32403431 Characteristic Analysis of Homo- and Heterodimeric Complexes of Human Mitochondrial Pyruvate Carrier Related to Metabolic Diseases

Lee, J, Jin, Z, Lee, W, Lee, D, Yun, JH

Int J Mol Sci 2020
22628558 A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans

Boutron, A, Boudina, S, Cox, JE, Rutter, J, Gygi, SP, Redin, C, Van Vranken, JG, Chen, YC, Taylor, EB, Thummel, CS, Cardon, CM, Dephoure, N, Orsak, T, Bricker, DK, Brivet, M, Schell, JC

Science 2012
Catalyst Activity

pyruvate transmembrane transporter activity of MPC dimer [mitochondrial inner membrane]

Inferred From
Cross References
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