Identification and Functional Expression of the Mitochondrial Pyruvate Carrier
Open accessAbstract
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 Herzig et al., 2012
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 [15]
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 [15]
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 Herzig et al., 2012
Coexpression of Mpc1 and Mpc2 in Lactococcus lactis induced a fourfold increase in pyruvate uptake.
“Indeed, Herzig et al. observed that coexpression of Mpc1 and Mpc2 in Lactococcus lactis induced a fourfold increase in pyruvate uptake (Herzig et al., 2012).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Herzig 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 Herzig 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 Herzig et al., 2012
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Self-citation
- Authors
- Herzig, S., Raemy, E., Montessuit, S., Veuthey, J.-L., Zamboni, N., Westermann, B., Kunji, E. R. S., & Martinou, J.-C.
- Affiliations
- University of Geneva (CH)
- Institute for Molecular Systems Biology (CH)
- University of Bayreuth (DE)
- MRC Mitochondrial Biology Unit (GB)
- Corresponding author
- Martinou, Jean-Claude
- ORCID
- Venue
- Science
- Published
- 2012-07-06
- Volume
- 337
- Issue
- 6090
- Pages
- 93-96
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2013334588
- Cited by
- 747
- References
- 26
- Citations by year
- 2026: 32 · 2025: 47 · 2024: 63 · 2023: 70 · 2022: 60 · 2021: 76 · 2020: 70 · 2019: 40 · 2018: 46 · 2017: 37 · 2016: 56 · 2015: 50 · 2014: 44 · 2013: 35 · 2012: 19
- FWCI
- 19.01
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- ERef Bayreuth (University of Bayreuth) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitochondrial pyruvate carrier, pyruvate transport, MPC1, MPC2, heterocomplexes, inner mitochondrial membrane, membrane proteins, Lactococcus lactis, yeast mutants
- MeSH terms
- Amino Acid Sequence, Animals, Biological Transport, Culture Media, Leucine, Thioctic Acid, Mitochondria, Molecular Sequence Data, Recombinant Proteins, Saccharomyces cerevisiae, Lactococcus lactis, Valine, Pyruvic Acid, Anion Transport Proteins, Monocarboxylic Acid Transporters, Saccharomyces cerevisiae Proteins, Mitochondrial Membrane Transport Proteins, Proprotein Convertase 1, Proprotein Convertase 2, Mitochondrial Membranes, Mice, Biosynthetic Pathways
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