Pyruvate is oxidized to acetyl‐CoA by pyruvate dehydrogenase which is localized in the mitochondrial matrix. The mitochondrial pyruvate carrier (MPC) is a hetero-oligomer composed of SLC54 family members (MPC1 and MPC2). The MPC is expressed in the inner mitochondrial membrane and involved in the import of pyruvate into mitochondria [1,5]. Ubiquitous disruption of either MPC1 or MPC2 expression results in embryonic lethality [7-8]. Clinically relevant concentrations of the insulin sensitizers, thiazolidinediones, specifically inhibit the MPC [3].

SLC54 family transporters appear to function as mechanisms for accumulating pyruvate into mitochondria to link glycolysis with oxidative phosphorylation.

* Key recommended reading is highlighted with an asterisk

Halestrap AP. (1975) The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J, 148 (1): 85-96. [PMID:1156402]

Koh E, Kim YK, Shin D, Kim KS. (2018) MPC1 is essential for PGC-1α-induced mitochondrial respiration and biogenesis. Biochem. J., 475 (10): 1687-1699. [PMID:29669911]

* McCommis KS, Finck BN. (2015) Mitochondrial pyruvate transport: a historical perspective and future research directions. Biochem J, 466 (3): 443-54. [PMID:25748677]

Nagampalli RSK, Quesñay JEN, Adamoski D, Islam Z, Birch J, Sebinelli HG, Girard RMBM, Ascenção CFR, Fala AM, Pauletti BA et al.. (2018) Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter. Sci Rep, 8 (1): 3510. [PMID:29472561]

Schell JC, Wisidagama DR, Bensard C, Zhao H, Wei P, Tanner J, Flores A, Mohlman J, Sorensen LK, Earl CS et al.. (2017) Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat. Cell Biol., 19 (9): 1027-1036. [PMID:28812582]

Tang XP, Chen Q, Li Y, Wang Y, Zou HB, Fu WJ, Niu Q, Pan QG, Jiang P, Xu XS et al.. (2019) Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the prognosis of human renal cell carcinoma. Lab. Invest., 99 (2): 191-199. [PMID:30291323]

Taylor EB. (2017) Functional Properties of the Mitochondrial Carrier System. Trends Cell Biol., 27 (9): 633-644. [PMID:28522206]

1. Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A, Chen YC, Cox JE, Cardon CM, Van Vranken JG, Dephoure N et al.. (2012) A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science, 337 (6090): 96-100. [PMID:22628558]

2. Colca JR, McDonald WG, Cavey GS, Cole SL, Holewa DD, Brightwell-Conrad AS, Wolfe CL, Wheeler JS, Coulter KR, Kilkuskie PM et al.. (2013) Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)--relationship to newly identified mitochondrial pyruvate carrier proteins. PLoS One, 8 (5): e61551. [PMID:23690925]

3. Divakaruni AS, Wiley SE, Rogers GW, Andreyev AY, Petrosyan S, Loviscach M, Wall EA, Yadava N, Heuck AP, Ferrick DA et al.. (2013) Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. Proc Natl Acad Sci U S A, 110 (14): 5422-7. [PMID:23513224]

4. Halestrap AP. (1975) The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J, 148 (1): 85-96. [PMID:1156402]

5. Herzig S, Raemy E, Montessuit S, Veuthey JL, Zamboni N, Westermann B, Kunji ER, Martinou JC. (2012) Identification and functional expression of the mitochondrial pyruvate carrier. Science, 337 (6090): 93-6. [PMID:22628554]

6. Vanderperre B, Cermakova K, Escoffier J, Kaba M, Bender T, Nef S, Martinou JC. (2016) MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells. J. Biol. Chem., 291 (32): 16448-61. [PMID:27317664]

7. Vanderperre B, Herzig S, Krznar P, Hörl M, Ammar Z, Montessuit S, Pierredon S, Zamboni N, Martinou JC. (2016) Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet. PLoS Genet, 12 (5): e1006056. [PMID:27176894]

8. Vigueira PA, McCommis KS, Schweitzer GG, Remedi MS, Chambers KT, Fu X, McDonald WG, Cole SL, Colca JR, Kletzien RF et al.. (2014) Mitochondrial pyruvate carrier 2 hypomorphism in mice leads to defects in glucose-stimulated insulin secretion. Cell Rep, 7 (6): 2042-2053. [PMID:24910426]