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Mitochondrial calcium uptake and release mechanisms as key regulators of cell life or death

De Marchi, Elena (2014) Mitochondrial calcium uptake and release mechanisms as key regulators of cell life or death. PhD Thesis , Università degli Studi di Ferrara.

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    Abstract

    Mitochondria are cellular organelles that play a key role in several physiological processes, including cell proliferation, differentiation, cell death and the regulation of cellular calcium (Ca2+) homeostasis. Increases in mitochondrial Ca2+ activate several dehydrogenases and carriers, inducing enhance in the respiratory rate, H+ extrusion, and ATP production necessary for the correct energy state of the cell. The mitochondrial Ca2+ uptake and release mechanisms are based on the utilization of gated channels for Ca2+ uptake and exchangers for release that are dependent upon the negative mitochondrial membrane potential, which represents the driving force for Ca2+ accumulation in the mitochondrial matrix. In this thesis, the attention was focused on two mechanisms in particular, the mitochondrial Ca2+ influx system by the activity of Mitochondrial Calcium Uniporter (MCU) complex, and the high-conductance channel mitochondrial Permeability Transition Pore (mPTP), responsible for a state of non-selective permeability of the inner mitochondrial membrane (IMM); its opening in non-physiological conditions leads to Ca2+ release from mitochondria and triggers cell death mechanisms. Thus the maintenance of the mitochondrial Ca2+ homeostasis is essential for a proper balance between cell life or death. In particular it will be discussed the possible involvement of MCU in the cell cycle, as the Ca2+ accumulation by MCU is important for the regulation of cell life and energy production. It will be shown that MCU is mainly expressed in specific phases of the cell cycle and this expression positive correlates with the mitochondrial membrane potential. MCU overexpression instead does not alter cell cycle phases. It will also described the role of the c subunit of Fo ATP synthase in mitochondrial permeability transition (MPT) and it will be demonstrated to be a critical component of the mPTP complex. Finally it will be discussed the role of mPTP in mitochondrial Ca2+ efflux and it will be shown that it is a dispensable element for mitochondrial Ca2+ efflux in non-pathological conditions.

    Item Type:Thesis (PhD Thesis)
    Date:28 March 2014
    Tutor:Pinton, Paolo - Wieckowski, Mariusz R.
    Coordinator:Bernardi, Francesco
    Institution:Università degli Studi di Ferrara
    PhD:XXVI Anno 2011 > BIOCHIMICA, BIOLOGIA MOLECOLARE E BIOTECNOLOGIE
    Divisions:Dipartimento > Scienze della vita e biotecnologie
    Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
    Uncontrolled Keywords:calcio, mitochondria, ciclo cellulare, permeability transition pore, mitochondrial calcuim uniporter
    Deposited on:01 Jul 2015 13:25

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