Characteristic analysis of homo- and heterodimeric complexes of human mitochondrial pyruvate carrier related to metabolic diseases

Jinyi Lee, Zeyu Jin, Donghan Lee, Ji Hye Yun, Weontae Lee

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8 Citations (Scopus)


Human mitochondrial pyruvate carriers (hMPCs), which are required for the uptake of pyruvate into mitochondria, are associated with several metabolic diseases, including type 2 diabetes and various cancers. Yeast MPC was recently demonstrated to form a functional unit of heterodimers. However, human MPC-1 (hMPC-1) and MPC-2 (hMPC-2) have not yet been individually isolated for their detailed characterization, in particular in terms of their structural and functional properties, namely, whether they exist as homo- or heterodimers. In this study, hMPC-1 and hMPC-2 were successfully isolated in micelles and they formed stable homodimers. However, the heterodimer state was found to be dominant when both hMPC-1 and hMPC-2 were present. In addition, as heterodimers, the molecules exhibited a higher binding capacity to both substrates and inhibitors, together with a larger structural stability than when they existed as homodimers. Taken together, our results demonstrated that the hetero-dimerization of hMPCs is the main functional unit of the pyruvate metabolism, providing a structural insight into the transport mechanisms of hMPCs.

Original languageEnglish
Article number3403
JournalInternational journal of molecular sciences
Issue number9
Publication statusPublished - 2020 May 1

Bibliographical note

Funding Information:
Funding: This work was supported by researcher Program (NRF-2019M3E5D6063903, 2017M3A9F6029753, 2018K2A9A2A06024227 to W. Lee and NRF-2016R1A6A3A04010213 to J.H. Yun) through the National Research Foundation of Korea. The work was supported in part by the Brain Korea 21(BK21) PLUS program/Z.J. are fellowship awardee by the BK21 PLUS program.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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