Lack of Oxygen Deactivates Mitochondrial Complex I IMPLICATIONS FOR ISCHEMIC INJURY?

Alexander Galkin, A.Y. Abramov, N. Frakich, M.R. Duchen, S. Moncada

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Abstract

For S-nitrosothiols and peroxynitrite to interfere with the activity of mitochondrial complex I, prior transition of the enzyme from its active (A) to its deactive, dormant (D) state is necessary. We now demonstrate accumulation of the D-form of complex I in human epithelial kidney cells after prolonged hypoxia. Upon reoxygenation after hypoxia there was an initial delay in the return of the respiration rate to normal. This was due to the accumulation of the D-form and its slow, substrate-dependent reconversion to the A-form. Reconversion to the A-form could be prevented by prolonged incubation with endogenously generated NO. We propose that the hypoxic transition from the A-form to the D-form of complex I may be protective, because it would act to reduce the electron burst and the formation of free radicals during reoxygenation. However, this may become an early pathophysiological event when NO-dependent formation of S-nitrosothiols or peroxynitrite structurally modifies complex I in its D-form and impedes its return to the active state. These observations provide a mechanism to account for the severe cell injury that follows hypoxia and reoxygenation when accompanied by NO generation.
Original languageEnglish
Pages (from-to)36055-36061
Number of pages7
JournalJournal of Biological Chemistry
Volume284
Issue number52
Early online date27 Oct 2009
DOIs
Publication statusPublished - 25 Dec 2009

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S-Nitrosothiols
Peroxynitrous Acid
Oxygen
Wounds and Injuries
Free Radicals
Respiratory Rate
Electrons
Substrates
Enzymes
Epithelial Cells
Kidney
Hypoxia

Cite this

Galkin, A., Abramov, A. Y., Frakich, N., Duchen, M. R., & Moncada, S. (2009). Lack of Oxygen Deactivates Mitochondrial Complex I IMPLICATIONS FOR ISCHEMIC INJURY? Journal of Biological Chemistry, 284(52), 36055-36061. https://doi.org/10.1074/jbc.M109.054346
Galkin, Alexander ; Abramov, A.Y. ; Frakich, N. ; Duchen, M.R. ; Moncada, S. / Lack of Oxygen Deactivates Mitochondrial Complex I IMPLICATIONS FOR ISCHEMIC INJURY?. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 52. pp. 36055-36061.
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Galkin, A, Abramov, AY, Frakich, N, Duchen, MR & Moncada, S 2009, 'Lack of Oxygen Deactivates Mitochondrial Complex I IMPLICATIONS FOR ISCHEMIC INJURY?', Journal of Biological Chemistry, vol. 284, no. 52, pp. 36055-36061. https://doi.org/10.1074/jbc.M109.054346

Lack of Oxygen Deactivates Mitochondrial Complex I IMPLICATIONS FOR ISCHEMIC INJURY? / Galkin, Alexander; Abramov, A.Y.; Frakich, N.; Duchen, M.R.; Moncada, S.

In: Journal of Biological Chemistry, Vol. 284, No. 52, 25.12.2009, p. 36055-36061.

Research output: Contribution to journalArticle

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