http://www.cnr.it/ontology/cnr/individuo/prodotto/ID322649

Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D (Articolo in rivista) (literal)

Anno

2012-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1016/j.bbabio.2012.05.011 (literal)

Alternative label

Li, Bo; Chauvin, Christiane; De Paulis, Damien; De Oliveira, Frederic; Gharib, Abdallah; Vial, Guillaume; Lablanche, Sandrine; Leverve, Xavier; Bernardi, Paolo; Ovize, Michel; Fontaine, Eric (2012)
Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D
in Biochimica et biophysica acta. Bioenergetics
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Li, Bo; Chauvin, Christiane; De Paulis, Damien; De Oliveira, Frederic; Gharib, Abdallah; Vial, Guillaume; Lablanche, Sandrine; Leverve, Xavier; Bernardi, Paolo; Ovize, Michel; Fontaine, Eric (literal)

Pagina inizio

1628 (literal)

Pagina fine

1634 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.ncbi.nlm.nih.gov/pubmed/22659400 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

1817 (literal)

Rivista

Biochimica et biophysica acta. Bioenergetics (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

7 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

9 (literal)

Note

ISI Web of Science (WOS) (literal)
Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Grenoble Univ Hosp; Consiglio Nazionale delle Ricerche (CNR); Hospices Civils de Lyon (literal)

Titolo

Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D (literal)

Abstract

Inhibition of the mitochondrial permeability transition pore (PTP) has proved to be an effective strategy for preventing oxidative stress-induced cell death, and the pore represents a viable cellular target for drugs. Here, we report that inhibition of complex I by rotenone is more effective at PTP inhibition than cyclosporin A in tissues that express low levels of the cyclosporin A mitochondrial target, cyclophilin D; and, conversely, that tissues in which rotenone does not affect the PTP are characterized by high levels of expression of cyclophilin D and sensitivity to cyclosporin A. Consistent with a regulatory role of complex I in the PTP-inhibiting effects of rotenone, the concentrations of the latter required for PTP inhibition precisely match those required to inhibit respiration; and a similar effect is seen with the antidiabetic drug metformin, which partially inhibits complex I. Remarkably (i) genetic ablation of cyclophilin D or its displacement with cyclosporin A restored PTP inhibition by rotenone in tissues that are otherwise resistant to its effects; and (ii) rotenone did not inhibit the PTP unless phosphate was present, in striking analogy with the phosphate requirement for the inhibitory effects of cyclosporin A [Basso et al. (2008) J. Biol. Chem. 283, 26307-26311]. These results indicate that inhibition of complex I by rotenone or metformin and displacement of cyclophilin D by cyclosporin A affect the PIP through a common mechanism; and that cells can modulate their PTP response to complex I inhibition by modifying the expression of cyclophilin D, a finding that has major implications for pore modulation in vivo. (C) 2012 Elsevier B.V. All rights reserved. (literal)

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