Harborne, SPD and Kunji, ERS (2018) Calcium‐regulated mitochondrial ATP‐Mg/Pi carriers evolved from a fusion of an EF‐hand regulatory domain with a mitochondrial ADP/ATP carrier‐like domain. IUBMB Life, 70 (12). pp. 1222-1232. ISSN 1521-6543
Abstract
The mitochondrial ATP‐Mg/Pi carrier is responsible for the calcium‐dependent regulation of adenosine nucleotide concentrations in the mitochondrial matrix, which allows mitochondria to respond to changing energy requirements of the cell. The carrier is expressed in mitochondria of fungi, plants and animals and belongs to the family of mitochondrial carriers. The carrier is unusual as it consists of three separate domains: (i) an N‐terminal regulatory domain with four calcium‐binding EF‐hands similar to calmodulin, (ii) a loop domain containing an amphipathic α‐helix and (iii) a mitochondrial carrier domain related to the mitochondrial ADP/ATP carrier. This striking example of three domains coming together from different origins to provide new functions represents an interesting quirk of evolution. In this review, we outline how the carrier was identified and how its physiological role was established with a focus on human isoforms. We exploit the sequence and structural information of the domains to explore the similarities and differences to their closest counterparts; mitochondrial ADP/ATP carriers and proteins with four EF‐hands. We discuss how their combined function has led to a mechanism for calcium‐regulated transport of adenosine nucleotides. Finally, we compare the ATP‐Mg/Pi carrier with the mitochondrial aspartate/glutamate carrier, the only other mitochondrial carrier regulated by calcium, and we will argue that they have arisen by convergent rather than divergent evolution.
Metadata
Item Type: | Article |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | transport; mitochondrion; metabolic energy generation; translocase; translocator; mitochondrial carrier; evolution |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Jul 2018 12:55 |
Last Modified: | 25 Jun 2023 21:27 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/iub.1931 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:133870 |