MPC1:MPC2 cotransports PYR, H+ from cytosol to mitochondrial matrix

Stable Identifier
R-HSA-372342
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial intermembrane space, mitochondrial inner membrane, mitochondrial matrix
Synonyms
PYR + H+ (cytosol) => PYR + H+ (mitochondrial matrix)
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MPC1:MPC2 cotransports PYR, H+ from cytosol to 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 1 and 2 (MCP1 and MCP2) located in the inner mitochondrial membrane (McCommis & Finck 2015). The proton gradient across the inner mitochondrial membrane must be maintained for ATP production to occur. Transport of PYR across this membrane would collapse this gradient therefore PYR is cotransported with H+. Studies of pyruvate uptake in rat 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. MCP1 and MCP2 have been identified as essential components of the transporter based on the observation that expression of both proteins (but not either one alone) restored mitochondrial pyruvate uptake in mutant budding yeast. The proteins form a multimeric complex; its stoichiometry is unknown (Bricker et al. 2012).

Literature References
PubMed ID Title Journal Year
11945601 The transport of pyruvate in rat liver mitochondria

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

FEBS Lett 1971
4822737 Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate

Halestrap, AP, Denton, RM

Biochem. J. 1974
22628558 A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans

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

Science 2012
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
pyruvate transmembrane transporter activity of MPC1:MPC2 [mitochondrial inner membrane]
Physical Entity
MPC1:MPC2 [mitochondrial inner membrane]
Activity
pyruvate transmembrane transporter activity (0050833)
Inferred From
Cytosolic PYR is transported to the mitochondrial matrix (Rattus norvegicus)
Cross References
Rhea
Authored
D'Eustachio, P  (2008-06-20)
Reviewed
Harris, RA  (2008-09-10)
Jassal, B  (2012-10-12)
Created
D'Eustachio, P  (2008-06-20)
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