http://www.cnr.it/ontology/cnr/individuo/prodotto/ID322965

Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons (Articolo in rivista)

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Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons (Articolo in rivista) (literal)

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Barsukova, Anna; Komarov, Alexander; Hajnoczky, Gyoergy; Bernardi, Paolo; Bourdette, Dennis; Forte, Michael (2011)
Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons
in European journal of neuroscience (Print)
(literal)

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Barsukova, Anna; Komarov, Alexander; Hajnoczky, Gyoergy; Bernardi, Paolo; Bourdette, Dennis; Forte, Michael (literal)

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1, 2, 6: Vollum Institute and Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; 3: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; 4: Department of Biomedical Sciences & CNR Institute of Neuroscience, University of Padova, Padova, Italy; 5: Department of Neurology, Oregon Health & Science University, Portland, OR, USA (literal)

Titolo

Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons (literal)

Abstract

The participation of mitochondria in cellular and neuronal Ca2+ homeostatic networks is now well accepted. Yet, critical tests of specific mitochondrial pathways in neuronal Ca2+ responses have been hampered because the identity of mitochondrial proteins that must be integrated within this dynamic system remain uncertain. One putative pathway for Ca2+ efflux from mitochondria exists through the formation of the permeability transition pore (PTP) that is often associated with cellular and neuronal death. Here, we have evaluated neuronal Ca2+ dynamics and the PTP in single adult neurons in wild-type mice and those missing cyclophilin D (CyPD), a key regulator of the PTP. Using high-resolution time-lapse imaging, we demonstrate that PTP opening only follows simultaneous activation with two physiological stimuli that generate critical threshold levels of cytosolic and mitochondrial Ca2+. Our results are the first to demonstrate CyPD-dependent PTP opening in normal neuronal Ca2+ homeostatic mechanisms not leading to activation of cell death pathways. As neurons in mice lacking CyPD are protected in a number of neurodegenerative disease models, the results suggest that improved viability of CyPD-knockout animals in these pathological states may be due to the transient, rather than persistent, activation of the PTP in mutant mitochondria, thereby shielding neurons from cytoplasmic Ca2+ overload. (literal)

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