4 December 2003. Reactive oxygen species (ROS) are well-established suspects in aging, atherosclerosis, and neurodegeneration. However, any therapeutic attempts to interfere with these short-lived molecules—which oxidize proteins, lipids, and nucleic acids in cells—will be well-advised to take into account the role of ROS in normal physiological processes in vivo. A paper in the December 5 issue of Science offers some clues about the manifold roles that ROS play in signaling pathways during embryonic development.
Yukimasa Shibata and others working with Siegfried Hekimi at McGill University in Montreal investigated the C. elegans mutant Clk-1, which fails to produce an enzyme necessary for biosynthesis of the electron carrier ubiquinone (coenzyme Q). Coenzyme Q, in turn, is involved in production for ROS. Added dietary CoQ allows the animal to survive, but the worm develops—and ages—too slowly, with delays in organ development and effects on behavior and reproduction. For example, decreased oxidation of LDL-like lipoproteins threw germline development into disarray.
The researchers found two signaling pathways by which this reduced redox chemistry affected development. One depends on reduced oxidation of an analog of vertebrate low-density lipoprotein (LDL) through Ack-related tyrosine kinase (ARK-1) and inositol trisphosphate signaling. The other is the ras pathway, which is altered via lowered cytoplasmic ROS levels.
"These findings provide a unique model to study the effect of redox signal transduction on the development of whole organisms and suggest a model for the Clk-1 pleiotropy, in which the complexity of the phenotype is due to the multiplicity of signaling roles that are carried out by the oxidative modification of cellular constituents," conclude the authors.
Do the molecular interactions described in this study have relevance to aging and neurodegenerative process? Let us know what you think.—Hakon Heimer.
Shibata Y, Branicky R, Oviedo Landaverde I, Hekimi S. Redox regulation of germline vulval development in Caenorhabditis elegans. Science. 2003 Dec 5;302(5651):1779-82.