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

Paul G Crichton (1) , Nadeene Parker , Antonio J Vidal-Puig , Martin D Brand

1 Mitochondrial Carriers

The mitochondrial permeability transition pore (mPTP) is a non-specific channel that forms in the mitochondrial inner membrane in response to several stimuli, including elevated levels of matrix calcium. The pore is proposed to be comprised of the adenine nucleotide translocase (ANT), 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 brown adipose tissue mitochondria in which levels of the mitochondrial carrier protein, uncoupling protein 1 (UCP1), can exceed those of ANT. Using an improved spectroscopic assay we have quantified mPTP formation in de-energised mitochondria from wild type and Ucp1 knockout mice and assessed the dependence of pore formation on UCP1. When correctly normalised 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 (~50% inhibited), although the portion sensitive to cyclosporin A is higher in mitochondria lacking UCP1 (~80% inhibited, compared to ~60% in mitochondria containing UCP1). We conclude that UCP1 is not a component of the cyclosporin A-sensitive mPTP in brown adipose tissue and that a role in mPTP formation is not a general characteristic of the mitochondrial carrier protein family but is more likely to be restricted to specific members including ANT.

Mots clés: Life Sciences

Paul G Crichton, Nadeene Parker, Antonio J Vidal-Puig, Martin D Brand. Not all mitochondrial carrier proteins support permeability transition pore formation: no involvement of uncoupling protein 1. Bioscience Reports, 2009, 30 (3), pp.187-192. ⟨10.1042/BSR20090063⟩. ⟨hal-00479316⟩