Not all mitochondrial carrier proteins support permeability transition pore formation: no involvement of uncoupling protein 1

Crichton, Paul G., Parker, Nadeene, Vidal-Puig, Antonio J. and Brand, Martin D. (2010) Not all mitochondrial carrier proteins support permeability transition pore formation: no involvement of uncoupling protein 1. Bioscience Reports, 30 (3). pp. 187-192. ISSN 0144-8463

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    Abstract

    The mPTP (mitochondrial permeability transition pore) is a non-specific channel that is formed in the mitochondrial inner membrane in response to several stimuli, including elevated levels of matrix calcium. The pore is proposed to be composed of the ANT (adenine nucleotide translocase), voltage-dependent anion channel and cyclophilin D. Knockout studies, however, have demonstrated that ANT is not essential for permeability transition, which has led to the proposal that other members of the mitochondrial carrier protein family may be able to play a similar function to ANT in pore formation. To investigate this possibility, we have studied the permeability transition properties of BAT (brown adipose tissue) mitochondria in which levels of the mitochondrial carrier protein, UCP1 (uncoupling protein 1), can exceed those of ANT. Using an improved spectroscopic assay, we have quantified mPTP formation in de-energized mitochondria from wild-type and Ucp1KO (Ucp1-knockout) mice and assessed the dependence of pore formation on UCP1. When correctly normalized for differences in mitochondrial morphology, we find that calcium-induced mPTP activity is the same in both types of mitochondria, with similar sensitivity to GDP (approximately 50% inhibited), although the portion sensitive to cyclosporin A is higher in mitochondria lacking UCP1 (approximately 80% inhibited, compared with approximately 60% in mitochondria containing UCP1). We conclude that UCP1 is not a component of the cyclosporin A-sensitive mPTP in BAT and that playing a role in mPTP formation is not a general characteristic of the mitochondrial carrier protein family but is, more likely, restricted to specific members including ANT.

    Item Type: Article
    Additional Information: © 2010 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    Related URLs:
    Depositing User: Pure Connector
    Date Deposited: 03 Nov 2016 11:00
    Last Modified: 25 Jul 2018 12:53
    URI: https://ueaeprints.uea.ac.uk/id/eprint/61216
    DOI: 10.1042/BSR20090063

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