Institut für Biochemie
Thielallee 63, 14195 Berlin; Tel. +49 30 838-52910, Fax -56509; E-mail: firstname.lastname@example.org
Keywords: mitochondria, ADP-ribosylation, cyclic ADP-ribose, Calcium signaling, membrane proteins.
Regulation of mitochondrial calcium fluxes by metabolites of NAD.
Mitochondria have been implicated in the regulation of cytosolic calcium levels. These organelles possess the ability to accumulate and release large amounts of calcium. Under "oxidative stress" mitochondrial NAD is degraded to ADP-ribose and nicotinamide and, concomitantly, calcium is released. Originally, the calcium release was proposed to be triggered by ADP-ribosylation of specific proteins related to a calcium channel. Our studies revealed that a mitochondrial enzyme, NAD glycohydrolase, may convert NAD to cyclic ADP-ribose. Cyclic ADP-ribose is a novel messenger molecule which exhibits intracellular calcium mobilizing activity as potently as inositol(1,4,5) trisphosphate (IP3). Our investigations are aimed at elucidating the role of mitochondrial formation of cyclic ADP-ribose and ADP-ribosylation by characterizing the enzymes and acceptor proteins involved.