Wolfgang F. Graier Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz Title Mitochondria: old guests new functions Abstract Mitochondria are ancient endosymbiotic guests that joined the cells in the evolution of complex life. While the unique ability of mitochondria to produce ATP and their contribution to cellular nutrition metabolism received condign attention, our understanding of the organelle’s contribution to Ca2+ homeostasis was restricted to serve as passive Ca2+ sinks that accumulate Ca2+ along the organelle’s negative membrane potential. This paradigm has changed radically. Nowadays, mitochondria are known to respond to environmental Ca2+ and to contribute actively to the regulation of spatial and temporal patterns of intracellular Ca2+ signaling. Accordingly, mitochondria contribute to many signal transduction pathways and are actively involved in the maintenance of capacitative Ca2+ entry, the accomplishment of Ca2+ refilling of the endoplasmic reticulum and Ca2+-dependent protein folding. Mitochondrial Ca2+ homeostasis is complex and regulated by numerous, so far, genetically unidentified Ca2+ channels, pumps and exchangers that concertedly accomplish the organelle’s Ca2+ demand. Notably, mitochondrial Ca2+ homeostasis and functions are crucially influenced by the organelle’s structural organization and motility that, in turn, is controlled by matrix/cytosolic Ca2+. Recently, intriguing results accumulated on the molecular mechanisms of mitochondrial Ca2+ homeostasis (uptake, buffering & storage, extrusion), its modulation by other ions, kinases and small molecules and its contribution to cellular processes as fundamental basis for the organelle’s contribution to signaling pathways. Hence, I shall introduce some current thoughts on the structure-to-function and mobility-to-function relationship of the mitochondria and, thereby, bridging our most recent knowledge on mitochondria with the best-established mitochondrial function: metabolism and ATP production. CV University education 1981-1988 Study of Pharmacy, University of Graz, Austria 1988-1991 Ph.D. in Pharmacology, Dept Pharmacology & Toxicology, Univ Graz, Austria 1993-1994 Post-graduate Education in Physiology, University of Missouri, Columbia, MO, USA Career history 1991-1993 Postdoctoral fellow, Department of Pharmacology & Toxicology, University of Graz, Austria 1993-1994 Postdoctoral training at the Dalton Cardiovascular Research Center, Vascular Cell Biophysics Laboratory: Prof. Dr. Mike Sturek, University of Missouri, Columbia, MO, USA 1994-1995 Assistant Professor at the Department of Medical Biochemistry, University of Graz, Austria 1995 Habilitation in Biochemical Pharmacology, Medical Faculty, University of Graz, Austria since 1995 Associate Professor, Depart. of Med Biochem & Med Molec Biol, Univ Graz, Austria 2001 Habilitation in Physiology, Medical Faculty, University of Graz, Austria since 2006 Head of the research unit for Molecular and Cellular Physiology at the Med Univ Graz Research interests Ca2+ signaling and Ca2+-dependent/-sensitive signaling pathways; mitochondria and ER functions; FRET-technology; fluorescence microscopy and electrophysiology, lipotoxicity Selected recent Publications on mitochondria Graier WF, Frieden M, Malli R (2007) Mitochondria and Ca signalling: old guests, new functions. Pflugers Arch (in press) Trenker, M., Malli, R., Fertschai, I., Sanja Levak-Frank, S. and Graier, W.F. 2007. Uncoupling-proteins 2 and 3 are elementary for mitochondrial Ca2+ uniport. Nat. Cell. Biol. 9: 445-452 Osibow, K., Frank, S., Malli, R., Zechner, R. and Graier, W.F. 2006. Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum. Biochem. J. 396: 173-182 Malli, R., Frieden, M., Trenker, M., and Graier, W.F. 2005. The role of mitochondria for Ca2+ refilling of the ER. J. Biol. Chem. 280:12114-12122 Paltauf-Doburzynska, J., Malli, R., and Graier, W.F. 2004. Hyperglycemic conditions affect shape and Ca2+ homeostasis of mitochondria in endothelial cells. J. Cardiovasc. Pharmacol. 44:424-437. Malli, R., Frieden, M., Osibow, K., and Graier, W.F. 2003. Mitochondria efficiently buffer subplasmalemmal Ca2+ elevation during agonist stimulation. J. Biol. Chem. 278:10807-10815 Institution address Ao. Univ.-Prof. Wolfgang F. Graier Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, A-8010 Graz phone: +43-316-380 7560, fax: +43-316-380 9615 wolfgang.graier@meduni-graz.at