Failure of apoptosis-inducing factor to act as neuroglobin reductase

Tommaso Moschetti (1) , Alessandro Giuffrè (1) , Chiara Ardiccioni (1) , Beatrice Vallone (1) , Nazanine Modjtahedi (2, 3, 4) , Guido Kroemer (2, 3, 4) , Maurizio Brunori (1)

1 CNR | IBPM - CNR Istituto di Biologia e Patologia Molecolari [Roma]
2 U848 - Apoptose, cancer et immunité
3 IGR - Institut Gustave Roussy
4 UP11 - Université Paris-Sud - Paris 11

Neuroglobin (Ngb) is a hexacoordinate globin expressed in the nervous system of vertebrates, where it protects neurons against hypoxia. Ferrous Ngb has been proposed to favor cell survival by scavenging NO and/or reducing cytochrome c released into the cytosol during hypoxic stress. Both catalytic functions require an as yet unidentified Ngb-reductase activity. Such an activity was detected both in tissue homogenates of human brain and liver and in Escherichia coli extracts. Since NADH:flavorubredoxin oxidoreductase from E. coli, that was shown to reduce ferric Ngb, shares sequence similarity with the human apoptosis-inducing factor (AIF), AIF has been proposed by us as a candidate Ngb reductase. In this study, we tested this hypothesis and show that the Ngb-reductase activity of recombinant human AIF is negligible and hence incompatible with such a physiological function.

Mots clés: Neuroprotection; Apoptosis; Hexacoordinate globins; Hypoxia; Enzymatic reduction; Electron transfer; Flavoproteins; Cytochrome c; Nitric oxide

Domaines: Sciences du Vivant [q-bio]

Tommaso Moschetti, Alessandro Giuffrè, Chiara Ardiccioni, Beatrice Vallone, Nazanine Modjtahedi, et al.. Failure of apoptosis-inducing factor to act as neuroglobin reductase. Biochemical and Biophysical Research Communications, 2009, 390 (1), pp.121-124. ⟨10.1016/j.bbrc.2009.09.078⟩. ⟨hal-02356576⟩