TRPM2, a dual function protein with ion channel and enzymatic domains, allows calcium entry to the cytosol in response to oxidative stress (1,2). In order to understand the mechanism through which TRPM2 channel gating is induced in response to cellular oxidant exposure, we have taken a combined approach involving structural, biochemical and electrophysiologic studies. The results from these studies suggest the existence of a novel oxidant-stress activated biochemical pathway which is localized to mitochondria, highly conserved evolutionarily, and which results in the production, release to the cytosol, and subsequent accumulation of free ADP-ribose sufficient to gate TRPM2 channels. Thus, production and release of free ADP-ribose represents a 2nd messenger mechanism through which mitochondria coordinate their function with cytosolic biochemistry during oxidative stress.
University of Glasgow (2004) J Physiol 557P, SA9
Research Symposium: Molecular analysis of oxidant-mediated TRPM2 activation
A.M. Scharenberg,A. Perraud,C.Takanishi,M.Smith and B. Shen
Pediatrics/Immunology, University of Washington, Seattle, WA, USA and Dept. of Basic Science, Fred Hutchinson Cancer Center, Seattle, WA, USA
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Where applicable, experiments conform with Society ethical requirements.