The yeast mitochondrial pyruvate carrier is a hetero-dimer in its functional state
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The mitochondrial pyruvate carrier (MPC) is critical for cellular homeostasis, as it is required in central metabolism for transporting pyruvate from the cytosol into the mitochondrial matrix. MPC has been implicated in many diseases and is being investigated as a drug target. A few years ago, small membrane proteins, called MPC1 and MPC2 in mammals and Mpc1, Mpc2 and Mpc3 in yeast, were proposed to form large protein complexes responsible for this function. However, the MPC complexes have never been isolated and their composition, oligomeric state and functional properties have not been defined. Here, we identify the functional unit of MPC from Saccharomyces cerevisiae . In contrast to earlier hypotheses, we demonstrate that MPC is a hetero‐dimer, not a multimeric complex. When not engaged in hetero‐dimers, the yeast Mpc proteins can also form homo‐dimers that are, however, inactive. We show that the earlier described substrate transport properties and inhibitor profiles are embodied by the hetero‐dimer. This work provides a foundation for elucidating the structure of the functional complex and the mechanism of substrate transport and inhibition.
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The MPC is a heterodimer composed of two subunits MPC1 and MPC2.
“This transporter is a heterodimer composed of two subunits MPC1 and MPC2 (Tavoulari et al., 2019).”
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 Tavoulari et al., 2019
The Results (Expression and purification of the yeast Mpc proteins) show that yeast Mpc1 and Mpc2 form a hetero-complex, but the paper selected Mpc1/Mpc3—not Mpc1/Mpc2—for direct determination of its dimeric state. The Discussion says the functional yeast carrier is a heterodimer and explicitly cautions that its results cannot safely establish the oligomeric state of mammalian MPCs. The unqualified claim therefore goes beyond what the paper establishes. (LLM, conf=0.87)
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Self-citation
- Authors
- Tavoulari, S., Thangaratnarajah, C., Mavridou, V., Harbour, M. E., Martinou, J., & Kunji, E. R.
- Affiliations
- University of Cambridge (GB)
- University of Geneva (CH)
- Corresponding author
- Tavoulari, Sotiria
- Kunji, Edmund RS
- ORCID
- Venue
- The EMBO Journal
- Published
- 2019-04-12
- Volume
- 38
- Issue
- 10
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC6517818
- OpenAlex
- W2939652298
- Cited by
- 73
- References
- 4
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 18 · 2019: 4
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- RCUK | Medical Research Council (MC_UU_00015/1)
- Oncosuisse (KFS‐4434‐02‐2018)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_179421/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial pyruvate carrier, pyruvate transport, heterodimer, oligomeric state, Saccharomyces cerevisiae, MPC1, MPC2, substrate transport mechanism, mitochondrial matrix
- MeSH terms
- Saccharomyces cerevisiae, Structure-Activity Relationship, Temperature, Gene Expression Regulation, Fungal, Pyruvic Acid, Protein Structure, Quaternary, Anion Transport Proteins, Monocarboxylic Acid Transporters, Saccharomyces cerevisiae Proteins, Organisms, Genetically Modified, Mitochondrial Membrane Transport Proteins, Multiprotein Complexes, Protein Multimerization
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