The mitochondrial ADP/ATP carrier exists and functions as a monomer
Biochemical Society Transactions
Portland Press, Ltd.
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Kunji, E., & Ruprecht, J. (2020). The mitochondrial ADP/ATP carrier exists and functions as a monomer. Biochemical Society Transactions, 48 (4), 1419-1432. https://doi.org/10.1042/BST20190933
For more than 40 years, the oligomeric state of members of the mitochondrial carrier family (SLC25) has been the subject of debate. Initially, the consensus was that they were dimeric, based on the application of a large number of different techniques. However, the structures of the mitochondrial ADP/ATP carrier, a member of the family, clearly demonstrated that its structural fold is monomeric, lacking a conserved dimerisation interface. A re-evaluation of previously published data, with the advantage of hindsight, concluded that technical errors were at the basis of the earlier dimer claims. Here, we revisit this topic, as new claims for the existence of dimers of the bovine ADP/ATP carrier have emerged using native mass spectrometry of mitochondrial membrane vesicles. However, the measured mass does not agree with previously published values, and a large number of post-translational modifications are proposed to account for the difference. Contrarily, these modifications are not observed in electron density maps of the bovine carrier. If they were present, they would interfere with the structure and function of the carrier, including inhibitor and substrate binding. Furthermore, the reported mass does not account for three tightly bound cardiolipin molecules, which are consistently observed in other studies and are important stabilising factors for the transport mechanism. The monomeric carrier has all of the required properties for a functional transporter and undergoes large conformational changes that are incompatible with a stable dimerisation interface. Thus, our view that the native mitochondrial ADP/ATP carrier exists and functions as a monomer remains unaltered.
Edmund Kunji and Jonathan Ruprecht would like to thank the Medical Research Council UK for funding (programme grant MC_UU_00015/1
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External DOI: https://doi.org/10.1042/BST20190933
This record's URL: https://www.repository.cam.ac.uk/handle/1810/307736
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/