Coenzyme Q10, plasma membrane oxidase and growth control.
The plasma membrane of eukaryotic cells contains an NADH oxidase which can transfer electrons across the membrane. This oxidase is controlled by hormones, growth factors and other ligands which bind to receptors in the plasma membrane. Oncogenes also affect activity of the oxidase. Natural serum components such as diferric transferrin and ceruloplasmin which stimulate proliferation also stimulate membrane oxidase activity. Additional growth factors can be required to complement the proliferative effect. Electron transport across the plasma membrane can be measured by the reduction of impermeable electron acceptors, such as ferricyanide, which also stimulate cell growth. The oxidants activate growth-related signals such as cytosolic alkalinization and calcium mobilization. Antiproliferative agents such as adriamycin and retinoic acid inhibit the plasma membrane electron transport. Flavin, Coenzyme Q and an iron chelate on the cell surface are apparent electron carriers for the transmembrane electron transport. Coenzyme Q10 stimulates cell growth, and Coenzyme Q analogs such as capsaicin and chloroquine reversibly inhibit both growth and transmembrane electron transport. Addition of iron salts to the depleted cells restores activity and growth. The ligand-activated oxidase in the plasma membrane introduces a new basis for control of signal transduction in cells. The redox state of the quinone in the oxidase is proposed to control tyrosine kinase either by generation of H2O2 or redox-induced conformational change.
Crane
F L
FL
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1392, USA.
Sun
I L
IL
Crowe
R A
RA
Alcain
F J
FJ
Löw
H
H
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D003067:Coenzymes; D004579:Electron Transport / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005057:Eukaryotic Cells / Q000201:enzymology / Q000502:physiology*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D010766:Phosphorylation; D010940:Plant Proteins / Q000502:physiology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000502:physiology; D015290:Second Messenger Systems; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology
D001426:Bacterial Proteins; D003067:Coenzymes; D006133:Growth Substances; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D010545:Peroxides; D010940:Plant Proteins; D017978:Receptors, Growth Factor; D014451:Ubiquinone; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C014227:ferricyanide reductase; D020794:Receptor Protein-Tyrosine Kinases; C024989:coenzyme Q10