The project addresses mitochondrial calcium (Ca2+) signalling and its regulation, with the aim of understanding how these events participate in the pathogenesis of mitochondrial disorders and can be targeted by novel drugs. Ca2+ is an important and complex messenger in the organelle, regulating processes as diverse as metabolic stimulation and pro-apoptotic structural alterations. In response to a large number of external stimuli, Ca2+ flows into the cell, and reaches mitochondria. Amplitude and timing of the Ca2+ flux (a sort of “Ca2+ signature”) determines an effect that can range from a number of cell activities (contraction, secretion, etc.) to its death. Dynamics and final outcome of mitochondrial Ca2+ signals depend on their 3D structure and other regulatory influences (kinases, redox state). The project i) utilizes a variety of experimental approaches for identifying the mitochondrial Ca2+ transporters and associated proteins, thus obtaining novel drug targets ii) investigates the regulatory mechanism that may operate in physiological and pathological conditions, focusing on redox state iii) analyses the mitochondrial Ca2+ effects of a specific mitochondrial disease, the Leber’s hereditary Optic Neuropathy (LHON). Preliminary studies indicate that this is a very promising line of research.
Mitochondrial calcium signalling and organelle dysfunction in mitochondrial diseases: molecular determinants and regulatory mechanisms
PINTON, Paolo
2007
Abstract
The project addresses mitochondrial calcium (Ca2+) signalling and its regulation, with the aim of understanding how these events participate in the pathogenesis of mitochondrial disorders and can be targeted by novel drugs. Ca2+ is an important and complex messenger in the organelle, regulating processes as diverse as metabolic stimulation and pro-apoptotic structural alterations. In response to a large number of external stimuli, Ca2+ flows into the cell, and reaches mitochondria. Amplitude and timing of the Ca2+ flux (a sort of “Ca2+ signature”) determines an effect that can range from a number of cell activities (contraction, secretion, etc.) to its death. Dynamics and final outcome of mitochondrial Ca2+ signals depend on their 3D structure and other regulatory influences (kinases, redox state). The project i) utilizes a variety of experimental approaches for identifying the mitochondrial Ca2+ transporters and associated proteins, thus obtaining novel drug targets ii) investigates the regulatory mechanism that may operate in physiological and pathological conditions, focusing on redox state iii) analyses the mitochondrial Ca2+ effects of a specific mitochondrial disease, the Leber’s hereditary Optic Neuropathy (LHON). Preliminary studies indicate that this is a very promising line of research.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
