Structural models of mitochondrial uncoupling proteins obtained in DPC micelles are not physiologically relevant for their uncoupling activity - Laboratoire de biologie physico-chimique des protéines membranaires Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2020

Structural models of mitochondrial uncoupling proteins obtained in DPC micelles are not physiologically relevant for their uncoupling activity

Résumé

Abstract Uncoupling protein 1 (UCP1) is found in the inner mitochondrial membrane of brown adipocyte. In the presence of long-chain fatty acids (LCFA), UCP1 increases the proton conductance, which, in turn, increases fatty acid oxidation and energy release as heat. Several atomic models of UCP1 and UCP2 have been obtained by NMR in dodecylphosphocholine (DPC), a detergent known to inactivate UCP1. Based on NMR titration experiment on UCP1 with LCFA, it has been proposed that K56 and K269 are crucial for LCFA binding and UCP1 activation. Given the numerous controversies on the use of DPC for structure-function analyses of membrane proteins, we revisited those UCP1 mutants in a more physiological context by expressing them in the mitochondria of S. cerevisiae . Mitochondrial respiration, assayed on permeabilized spheroplasts, enables the determination of UCP1 activation and inhibition. The K56S, K269S and K56S/K269S mutants did not display any default in activation, which shows that the NMR experiments in DPC detergent are not relevant to understand UCP1 function.
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Dates et versions

hal-04019245 , version 1 (08-03-2023)

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Mathilde Piel, Sandrine Masscheleyn, Frédéric Bouillaud, Karine Moncoq, Bruno Miroux. Structural models of mitochondrial uncoupling proteins obtained in DPC micelles are not physiologically relevant for their uncoupling activity. 2023. ⟨hal-04019245⟩
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