Institut für Biochemie
Thielallee 63, 14195 Berlin; Tel. +49 30 838-52910, Fax -56509;
E-mail:
mziegler@chemie.fu-berlin.de
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.
© 1996, Redaktionsschluß: 1996-08-01.