Inhibition of Cytochrome-C Oxidase Activity During Prolonged Hypoxia

Am J Physiol. 1995 Jun;268(6 Pt 1):L918-25. doi: 10.1152/ajplung.1995.268.6.L918.


During acute (< 30 min) hypoxia, cellular respiration is independent of the O2 concentration as long as PO2 remains above a critical value (5-10 Torr). Similarly, state 3 respiration by isolated mitochondria is independent of PO2 above a critical tension of 2-4 Torr. However, rat hepatocytes demonstrate a reversible suppression of respiration and an increase in NAD(P)H concentration during prolonged (2-24 h), but not acute hypoxia [P. T. Schumacker, N. Chandel, and A. G. N. Augusti. Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L395-L402, 1993]. This study tested whether respiration is similarly inhibited in isolated mitochondria exposed to low PO2 for prolonged periods and whether cytochrome-c oxidase participates in this response. Coupled rat liver mitochondria were incubated under low oxygen conditions (PO2 < 2 Torr) for 2 h. State 3 respiration after reoxygenation to PO2 = 20 Torr was then compared with the value obtained subsequently at 100 Torr. Using succinate and ADP as substrates, we determined that state 3 respiration at 20 Torr was 61.0 +/- 8.4% of the subsequent value at 100 Torr (P < 0.05). By contrast, control mitochondria reoxygenated to 100 Torr first and 20 Torr subsequently showed no significant difference at the two O2 tensions (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcimycin / pharmacology
  • Cell Hypoxia
  • Electron Transport Complex IV / antagonists & inhibitors*
  • Kinetics
  • Male
  • Mitochondria, Liver / enzymology*
  • Mitochondria, Liver / metabolism
  • Oxidative Phosphorylation
  • Oxygen / pharmacology
  • Oxygen Consumption / drug effects
  • Partial Pressure
  • Rats
  • Rats, Sprague-Dawley


  • Calcimycin
  • Electron Transport Complex IV
  • Oxygen