PMID- 17164295 OWN - NLM STAT- MEDLINE DCOM- 20070404 LR - 20131121 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 120 IP - Pt 1 DP - 2007 Jan 1 TI - Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxide. PG - 160-5 AB - Nitric oxide (NO), generated endogenously in NO-synthase-transfected cells, increases the reduction of mitochondrial cytochrome c oxidase (CcO) at O2 concentrations ([O2]) above those at which it inhibits cell respiration. Thus, in cells respiring to anoxia, the addition of 2.5 microM L-arginine at 70 microM O2 resulted in reduction of CcO and inhibition of respiration at [O2] of 64.0+/-0.8 and 24.8+/-0.8 microM, respectively. This separation of the two effects of NO is related to electron turnover of the enzyme, because the addition of electron donors resulted in inhibition of respiration at progressively higher [O2], and to their eventual convergence. Our results indicate that partial inhibition of CcO by NO leads to an accumulation of reduced cytochrome c and, consequently, to an increase in electron flux through the enzyme population not inhibited by NO. Thus, respiration is maintained without compromising the bioenergetic status of the cell. We suggest that this is a physiological mechanism regulated by the flux of electrons in the mitochondria and by the changing ratio of O2:NO, either during hypoxia or, as a consequence of increases in NO, as a result of cell stress. FAU - Palacios-Callender, Miriam AU - Palacios-Callender M AD - Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK. FAU - Hollis, Veronica AU - Hollis V FAU - Frakich, Nanci AU - Frakich N FAU - Mateo, Jesus AU - Mateo J FAU - Moncada, Salvador AU - Moncada S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061212 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Cytochrome c Group) RN - 0 (Cytochromes a3) RN - 0 (cytochrome caa(3)) RN - 31C4KY9ESH (Nitric Oxide) RN - 9035-34-1 (Cytochromes a) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.9.3.1 (Electron Transport Complex IV) RN - S88TT14065 (Oxygen) SB - IM MH - Arginine/metabolism/pharmacology MH - Cell Hypoxia/*physiology MH - Cell Line MH - Cell Respiration/drug effects/physiology MH - Cytochrome c Group/metabolism MH - Cytochromes a/metabolism MH - Cytochromes a3/metabolism MH - Electron Transport/physiology MH - Electron Transport Complex IV/*metabolism MH - Humans MH - Mitochondria/*enzymology MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase/genetics/metabolism MH - Oxygen/metabolism MH - Oxygen Consumption/drug effects/physiology MH - Transfection EDAT- 2006/12/14 09:00 MHDA- 2007/04/05 09:00 CRDT- 2006/12/14 09:00 PHST- 2006/12/14 09:00 [pubmed] PHST- 2007/04/05 09:00 [medline] PHST- 2006/12/14 09:00 [entrez] AID - jcs.03308 [pii] AID - 10.1242/jcs.03308 [doi] PST - ppublish SO - J Cell Sci. 2007 Jan 1;120(Pt 1):160-5. doi: 10.1242/jcs.03308. Epub 2006 Dec 12.