Failure of apoptosis-inducing factor to act as neuroglobin reductase

• Published in: Biochemical and biophysical research communications Vol. 390; no. 1; pp. 121 - 124
• Main Authors: Moschetti, Tommaso, Giuffrè, Alessandro, Ardiccioni, Chiara, Vallone, Beatrice, Modjtahedi, Nazanine, Kroemer, Guido, Brunori, Maurizio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.12.2009; Elsevier
• Subjects: Animals; Apoptosis; Apoptosis Inducing Factor - chemistry; Apoptosis Inducing Factor - genetics; Apoptosis Inducing Factor - metabolism; Brain - enzymology; Cytochrome c; Electron transfer; Enzymatic reduction; Escherichia coli; Flavoproteins; Globins - chemistry; Globins - genetics; Globins - metabolism; Hexacoordinate globins; Humans; Hypoxia; Life Sciences; Liver - enzymology; Mice; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuroglobin; Neuroprotection; Nitric oxide; Oxidation-Reduction; Oxidoreductases - chemistry; Oxidoreductases - genetics; Oxidoreductases - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Ctag-AIF; Neuroprotection; Ngb(FeIII); FlRd-red; Enzymatic reduction; Ngb; Electron transfer; Ngb(FeII); Cytochrome c; NCtag-AIF; Nitric oxide; Hypoxia; Cyt-c; Hexacoordinate globins; Flavoproteins; AIF; Apoptosis
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2009.09.078

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.