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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.