The evolution of coenzyme Q.
In the 50 years since the identification of coenzyme Q as an electron carrier in mitochondria, it has been identified with diverse and unexpected functions in cells. Its discovery came as a result of a search for electron carriers in mitochondria following the identification of flavin and cytochromes by Warburg, Keilin, Chance and others. As a result of investigation of membrane lipids at D.E. Green's laboratory at University of Wisconsin coenzyme Q was identified as the electron carrier between primary flavoprotein dehydrogenases and the cytochromes. Then Peter Mitchell identified the role of transmembrane proton transfer as a basis for ATP synthesis. The general distribution of coenzyme Q in all cell membranes then led to the recognition of a role as a primary antioxidant. The protonophoric function was extended to acidification of Golgi and lysosomal vericles. A further role in proton release through the plasma membrane and its relation to cell proliferation has not been fully developed. A role in generation of H202 as a messenger for hormone and cytokine action is indicated as well as prevention of apoptosis by inhibition of ceramide release. Identification of the genes and proteins required for coenzyme Q synthesis has led to a basis for defining deficiency. For 50 years Karl Folkers has led the search for deficiency and therapeutic application. The development of large scale production, better formulation for uptake, and better methods for analysis have furthered this search. The story isn't over yet. Questions remain about effects on membrane structure, breakdown and control of cellular synthesis and uptake and the basis for therapeutic action.
Crane
Frederick L
FL
Department of Biological Science, Purdue University, West Lafayette, IN, USA. flccoq10@aol.com
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004579:Electron Transport; D044927:Electron-Transferring Flavoproteins / Q000502:physiology; D006801:Humans; D051336:Mitochondrial Membranes / Q000502:physiology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000502:physiology / Q000627:therapeutic use
D044927:Electron-Transferring Flavoproteins; D014451:Ubiquinone; C024989:coenzyme Q10