A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila , and Humans
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Letting Pyruvate In: Transport of pyruvate is an important event in metabolism whereby the pyruvate formed in glycolysis is transported into mitochondria to feed into the tricarboxylic acid cycle (see the Perspective by Murphy and Divakaruni ). Two groups have now identified proteins that are components of the mitochondrial pyruvate transporter. Bricker et al. (p. 96 , published online 24 May) found that the proteins mitochondrial pyruvate carrier 1 and 2 (MPC1 and MPC2) are required for full pyruvate transport in yeast and Drosophila cells and that humans with mutations in MPC1 have metabolic defects consistent with loss of the transporter. Herzig et al. (p. 93 , published online 24 May) identified the same proteins as components of the carrier in yeast. Furthermore, expression of the mouse proteins in bacteria conferred increased transport of pyruvate into bacterial cells.
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Pyruvate is imported into mitochondria through the mitochondrial pyruvate carrier (MPC).
“Pyruvate, the end product of glycolysis, is imported into mitochondria through the mitochondrial pyruvate carrier (MPC) (Bricker et al., 2012; Herzig et al., 2012).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Bricker et al., 2012
In normoxia, pyruvate is generated via glycolysis and transported across the IMM through the Mitochondrial Pyruvate Carrier, then catabolized inside mitochondria through the TCA cycle.
“In normoxia, pyruvate is generated via glycolysis and transported across the IMM through the Mitochondrial Pyruvate Carrier (MPC).15,16 Pyruvate is further catabolized inside mitochondria through the TCA cycle.”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [16]
Pharmacological inhibition of MPC represses mitochondrial pyruvate uptake, shifting reliance to glycolysis for ATP production.
“Pharmacological inhibition of MPC represses mitochondrial pyruvate uptake, shifting reliance to glycolysis for ATP production.”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [16]
The genes MPC1 and MPC2 encode the multimeric mitochondrial pyruvate carrier (MPC) complex embedded in the mitochondrial inner membrane.
“Two recent studies revealed strong evidence that the genes, renamed MPC1 and MPC2, encode the multimeric mitochondrial pyruvate carrier (MPC) complex embedded in the mitochondrial inner mitochondrial membrane (Bricker et al., 2012; Herzig et al., 2012).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Bricker et al., 2012
These results are consistent with the severe growth defect previously observed in yeast with deletions in both mpc1 and mitochondrial malic enzyme growing on glucose.
“These results are consistent with the severe growth defect previously observed in yeast with deletions in both mpc1 and mitochondrial malic enzyme growing on glucose (Bricker et al., 2012), highlighting the remarkably conserved nature of metabolism across species.”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Bricker et al., 2012
MPC1 and MPC2 are components of the mitochondrial pyruvate transporter.
“Our analyses also more explicitly delineate the roles of MPC1 and MPC2 as components of the mitochondrial pyruvate transporter.”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Bricker et al., 2012
Bricker et al. and Herzig et al. both observed growth defects in medium lacking leucine or valine in their characterizations of yeast with Mpc deletions.
“Consistent with this change, Bricker et al. (Bricker et al., 2012) and Herzig et al. (Herzig et al., 2012) both observed growth defects in medium lacking leucine or valine in their characterizations of yeast with Mpc deletions.”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Bricker et al., 2012
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- Authors
- Bricker, D. K., Taylor, E. B., Schell, J. C., Orsak, T., Boutron, A., Chen, Y.-C., Cox, J. E., Cardon, C. M., Van Vranken, J. G., Dephoure, N., Redin, C., Boudina, S., Gygi, S. P., Brivet, M., Thummel, C. S., & Rutter, J.
- Affiliations
- University of Utah (US)
- Assistance Publique – Hôpitaux de Paris (FR)
- Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
- Harvard University (US)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Corresponding author
- Bricker, Daniel K.
- Taylor, Eric B.
- Schell, John C.
- Orsak, Thomas
- Rutter, Jared
- ORCID
- Venue
- Science
- Published
- 2012-07-06
- Volume
- 337
- Issue
- 6090
- Pages
- 96-100
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3690818
- OpenAlex
- W2019750161
- Cited by
- 843
- References
- 19
- Citations by year
- 2026: 36 · 2025: 60 · 2024: 68 · 2023: 77 · 2022: 70 · 2021: 81 · 2020: 76 · 2019: 58 · 2018: 57 · 2017: 48 · 2016: 52 · 2015: 46 · 2014: 57 · 2013: 38 · 2012: 17
- FWCI
- 20.33
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health (2r01dk071962-05a1)
- National Heart, Lung, and Blood Institute (P30HL101310)
- National Institute of General Medical Sciences (R01GM083746, R01GM087346, T32GM007464, R01GM094232)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072437, RC1DK086426, R01 DK-071962, R24DK092784)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K99AR059190)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitochondrial pyruvate carrier, MPC1, MPC2, pyruvate uptake, pyruvate oxidation, TCA cycle, inner mitochondrial membrane, lactic acidosis, carbon metabolism, yeast, Drosophila, human
- MeSH terms
- Amino Acid Sequence, Amino Acids, Animals, Biological Transport, Citric Acid Cycle, Drosophila melanogaster, Humans, Mitochondria, Molecular Sequence Data, Oxidation-Reduction, Saccharomyces cerevisiae, Point Mutation, Pyruvic Acid, Mitochondrial Proteins, Anion Transport Proteins, Monocarboxylic Acid Transporters, Saccharomyces cerevisiae Proteins, Drosophila Proteins, Mitochondrial Membrane Transport Proteins, Carbohydrate Metabolism, Mitochondrial Membranes, Metabolomics
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