OBJECTIVES

• This group has spent many years doing quality research in the biomedical field, backed by numerous publications in international impact magazines. Based on this previous history, we now intend to constitute ourselves as a GIR in order to continue our investigative work within the new framework created by the University Statutes of 2003. The general objective of our group is to investigate the role of calcium as a second messenger to cellular and subcellular level, with special emphasis on the mitochondria as a key organelle in the control of calcium metabolism and its physiological effects. Our group has studied in the last 10 years various aspects of the contribution of the endoplasmic reticulum and mitochondria to the genesis of the Ca2 + signal in different types of cells. In particular, measurements of mitochondrial Ca2 + in bovine chromaffin cells marked a very important milestone in showing that these mitochondria were capable of physiologically and rapidly reversible tremendous increases in calcium. In this work, published in the prestigious journal Nature Cell Biology in 2000, we further demonstrate that the uptake of Ca2 + by mitochondria regulates the rate of catecholamine secretion in chromaffin cells. This finding allowed us to postulate the ability of mitochondria to modulate cytosolic Ca2 + dependent phenomena. This new mitochondrial function may be of great importance in the development of various diseases that are believed to have originated in progressive mitochondrial alteration with age, due to oxidative damage. In fact, the implication of mitochondrial alterations in the development of Alzheimer's, Parkinson's and Huntington's diseases has been suggested. Furthermore, the entry of Ca2 + into the mitochondria has been shown to be an essential factor in the control of insulin secretion and can play a very important physiological role also in the regulation of cardiac contraction. Our group is currently studying the system responsible for the uptake of Ca2 + by mitochondria, the mitochondrial Ca2 + uniporter, which is one of the great unknown of mitochondrial physiology. We have obtained pharmacological evidence in recent years that mitochondrial Ca2 + uptake is strongly regulated, and we have shown that there are a number of natural compounds of plant origin that produce potent activation of said Ca2 + uptake by mitochondria. On the other hand, we are also investigating the presence of alterations in mitochondrial calcium transport in diseases due to alterations in mitochondrial DNA, and we are keeping open additional lines of research regarding Ca2 + homeostasis in other organelles (nucleus, endoplasmic reticulum, vesicles secretion) and the pathophysiological implications of alterations in subcellular Ca2 + dynamics.

RESEARCH LINES

• Regulation of mitochondrial Ca2 + transport

• Pathophysiological implications of alterations in Ca2 + homeostasis in the mitochondria.

• Role of mitochondrial Ca2 + in diseases due to alterations in mitochondrial DNA

• Ca2 + ion dynamics in other organelles: endoplasmic reticulum and secretion vesicles.