Coenzyme Q10, plasma membrane oxidase and growth control

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Eukaryotic cells possess a plasma membrane NADH oxidase involved in transmembrane electron transport.
• This oxidase's activity is modulated by hormones, growth factors, oncogenes, and serum components, influencing cell proliferation.
• Transmembrane electron transport is linked to crucial cellular signals like cytosolic alkalinization and calcium mobilization.

Purpose of the Study:

• To investigate the role of plasma membrane NADH oxidase in cell signaling and growth regulation.
• To identify electron carriers involved in transmembrane electron transport.
• To explore the oxidase's potential control over tyrosine kinase activity.

Main Methods:

• Measuring plasma membrane electron transport via reduction of impermeable electron acceptors (e.g., ferricyanide).
• Assessing the effects of various ligands, growth factors, serum components, and inhibitors on oxidase activity and cell growth.
• Investigating the role of specific electron carriers like flavin, Coenzyme Q, and iron chelates.

Main Results:

• Hormones, growth factors, and serum components stimulate both membrane oxidase activity and cell proliferation.
• Antiproliferative agents inhibit plasma membrane electron transport.
• Coenzyme Q10 and iron salts were found to be crucial for oxidase activity and cell growth, while analogs inhibited these processes.

Conclusions:

• The ligand-activated plasma membrane oxidase represents a novel mechanism for controlling cellular signal transduction.
• The redox state of the oxidase's quinone is proposed to regulate tyrosine kinase activity through hydrogen peroxide generation or conformational changes.
• This pathway offers new insights into cell growth regulation and potential therapeutic targets.