Failure of apoptosis-inducing factor to act as neuroglobin reductase.
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.
Department of Biochemical Sciences and CNR Institute of Molecular Biology and Pathology, Sapienza University of Rome, I-00185 Rome, Italy.
Tommaso
T
Moschetti
Alessandro
A
Giuffrè
Chiara
C
Ardiccioni
Beatrice
B
Vallone
Nazanine
N
Modjtahedi
Guido
G
Kroemer
Maurizio
M
Brunori
D000818:Animals; D051033:Apoptosis Inducing Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000201:enzymology; D004926:Escherichia coli; D005914:Globins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D011994:Recombinant Proteins; D005914:Globins; D010088:Oxidoreductases