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Characteristic Analysis of Homo- and Heterodimeric Complexes of Human Mitochondrial Pyruvate Carrier Related to Metabolic Diseases.
- Source :
-
International Journal of Molecular Sciences . May2020, Vol. 21 Issue 9, p3403-3403. 1p. 1 Diagram, 5 Graphs. - Publication Year :
- 2020
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *METABOLIC disorders
*HOMODIMERS
*TYPE 2 diabetes
*HETERODIMERS
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 21
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 143494915
- Full Text :
- https://doi.org/10.3390/ijms21093403