A role for neuroglobin: resetting the trigger level for apoptosis in neuronal and retinal cells.

Abstract:

:We propose a new hypothesis for the molecular mechanism by which neuroglobin exerts its protective effect in hypoxia-induced cell death. Our recent observation of a very rapid electron-transfer reaction between ferrous neuroglobin and ferric cytochrome c is central to this hypothesis. In contrast to previously suggested roles for neuroglobin, related to its putative but unlikely oxygen storage/transport properties or its ability to react with nitrogen oxides, we suggest that ferrous neuroglobin exerts its protective effect via modulation of the early events in the intrinsic apoptotic pathway. We suggest this is achieved by the rapid reduction of cytosolic ferric cytochrome c by neuroglobin. The maintenance of cytochrome c in the nonapoptotic ferrous oxidation state and the concomitant generation of ferric neuroglobin in this reaction fit well with known feedback processes in the early events of the intrinsic apoptotic pathway. Our hypothesis also fits well with a number of previously uncorrelated findings, including the localization of neuroglobin in close proximity to mitochondria, the high concentration of neuroglobin in cells whose basal rates of aerobic metabolism are extremely high, and the cell types which are subject to large calcium ion fluxes in their normal physiology.

journal_name

IUBMB Life

journal_title

IUBMB life

authors

Fago A,Mathews AJ,Brittain T

doi

10.1002/iub.35

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

398-401

issue

6

eissn

1521-6543

issn

1521-6551

journal_volume

60

pub_type

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