Article

Download article 		Title: Mitochondria generated nitric oxide protects against permeability transition via formation of membrane protein S-nitrosothiols
Author: Leite, Ana Catarina R.; Oliveira, Helena C.F.; Utino, Fabiane L.; Garcia, Rafael; Alberici, Luciane C.; Fernandes, Mariana P.; Castilho, Roger F.; Vercesi, Aníbal E.
Year: 2010
Is part of: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v. 1797, p. 1210 - 1216
DOI: https://doi.org/10.1016/j.bbabio.2010.01.034

Citation: Leite, Ana Catarina R.; Oliveira, Helena C.F.; Utino, Fabiane L.; Garcia, Rafael; Alberici, Luciane C.; Fernandes, Mariana P.; Castilho, Roger F.; Vercesi, Aníbal E.; Mitochondria generated nitric oxide protects against permeability transition via formation of membrane protein S-nitrosothiols. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v.1797, p. 1210-1216, 2010

Abstract: Mitochondria generated nitric oxide (NO center dot) regulates several cell functions including energy metabolism, cell cycling, and cell death. Here we report that the NO center dot synthase inhibitors (L-NAME, L-NNA and L-NMMA) administered either in vitro or in vivo induce Ca2+-dependent mitochondrial permeability transition (MPT) in rat liver mitochondria via a mechanism independent on changes in the energy state of the organelle. MPT was determined by the occurrence of cyclosporin A sensitive mitochondrial membrane potential disruption followed by mitochondrial swelling and Ca2+ release. In in vitro experiments, the effect of NOS inhibitors was dose-dependent (1 to 50 mu M). In addition to cyclosporin A, L-NAME-induced MPT was sensitive to Mg2+ plus ATP, EGTA, and to a lower degree, to catalase and dithiothreitol. In contrast to L-NAME, its isomer D-NAME did not induce MPT. L-NAME-induced MPT was associated with a significant decrease in both the rate of NO center dot generation and the content of mitochondrial S-nitrosothiol. Acute and chronic in vivo treatment with L-NAME also promoted MPT and decreased the content of mitochondrial S-nitrosothiol. SNAP (a NO center dot donor) prevented L-NAME mediated MPT and reversed the decrease in the rate of NO center dot generation and in the content of S-nitrosothiol. We propose that S-nitrosylation of critical membrane protein thiols by NO center dot protects against MPT. (C) 2010 Elsevier B.V. All rights reserved.

Keywords: mitochondria permeability transition; nitric oxide; nitric oxide synthase; S-nitrosothiol;
Subjects: CIENCIAS_BIOLOGICAS; Metabolismo e Bioenergética; CIENCIAS_BIOLOGICAS; Bioquímica; Metabolismo e Bioenergética; Bioenergética Mitocondrial; 		Financed by: