Mitochondria are dynamic, semi-autonomous organelles surrounded by a double membrane that have their own genome and protein synthesis machinery. In addition to being the major source of ATP in eukaryotes, they are the site of many important metabolic reactions such as the urea cycle, lipid metabolism, steroid hormone and porphyrin synthesis and interconversion of amino acids. Moreover, mitochondria play a central role in complex physiological processes including cellular proliferation, differentiation, apoptosis and in cellular processes like glucose sensing/insulin regulation and cellular Ca2+ homeostasis. It is therefore not surprising that mitochondrial dysfunctions have been found to be associated with several diseases such as neurodegenerative diseases, aging and cancer. In this work, we investigate on the relationship between mitochondrial dynamics and two of the main research priorities in the world: cancer and neurodegenerative disease. In particular, we have addressed: - i) The role of the PKCβ and mitochondrial physiology in the modulation of autophagy, a major phenomenon of cell biology, which acts as a pro-survival or pro-death mechanism and takes part in different biological events. - ii) The identification of a microRNA (miR-25), highly expressed in cancer cells, that by targeting the newly discovered calcium channel of mitochondria (Mitochondrial Calcium Uniporter) reduces the sensitivity of cancer cells to apoptotic agents. - iii) How, one of the most important cytokines for the aetiology of Multiple Sclerosis, TNFα, lead to alteration of the mitochondrial bioenergetics, with a consequent impairment of oligodendrocytes differentiation In conclusion, these findings reveal new relations between mitochondria, calcium signalling and cell physiology, shedding new light on the role for this fascinating organelle.

Mitochondrial dysfunctions in cancer and neurodegenerative disease

PATERGNANI, Simone
2013

Abstract

Mitochondria are dynamic, semi-autonomous organelles surrounded by a double membrane that have their own genome and protein synthesis machinery. In addition to being the major source of ATP in eukaryotes, they are the site of many important metabolic reactions such as the urea cycle, lipid metabolism, steroid hormone and porphyrin synthesis and interconversion of amino acids. Moreover, mitochondria play a central role in complex physiological processes including cellular proliferation, differentiation, apoptosis and in cellular processes like glucose sensing/insulin regulation and cellular Ca2+ homeostasis. It is therefore not surprising that mitochondrial dysfunctions have been found to be associated with several diseases such as neurodegenerative diseases, aging and cancer. In this work, we investigate on the relationship between mitochondrial dynamics and two of the main research priorities in the world: cancer and neurodegenerative disease. In particular, we have addressed: - i) The role of the PKCβ and mitochondrial physiology in the modulation of autophagy, a major phenomenon of cell biology, which acts as a pro-survival or pro-death mechanism and takes part in different biological events. - ii) The identification of a microRNA (miR-25), highly expressed in cancer cells, that by targeting the newly discovered calcium channel of mitochondria (Mitochondrial Calcium Uniporter) reduces the sensitivity of cancer cells to apoptotic agents. - iii) How, one of the most important cytokines for the aetiology of Multiple Sclerosis, TNFα, lead to alteration of the mitochondrial bioenergetics, with a consequent impairment of oligodendrocytes differentiation In conclusion, these findings reveal new relations between mitochondria, calcium signalling and cell physiology, shedding new light on the role for this fascinating organelle.
PINTON, Paolo
BERNARDI, Francesco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2388846
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