Artículo

Martinez, J.H.; Alaimo, A.; Gorojod, R.M.; Porte Alcon, S.; Fuentes, F.; Coluccio Leskow, F.; Kotler, M.L. "Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein" (2018) Molecular and Cellular Neuroscience. 88:107-117
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Abstract:

Parkinson's disease is a neurodegenerative movement disorder caused by the loss of dopaminergic neurons from substantia nigra. It is characterized by the accumulation of aggregated α-synuclein as the major component of the Lewy bodies. Additional common features of this disease are the mitochondrial dysfunction and the activation/inhibition of autophagy both events associated to the intracellular accumulation of α-synuclein. The mechanism by which these events contribute to neural degeneration remains unknown. In the present work we investigated the effect of α-synuclein on mitochondrial dynamics and autophagy/mitophagy in SH-SY5Y cells, an in vitro model of Parkinson disease. We demonstrated that overexpression of wild type α-synuclein causes moderated toxicity, ROS generation and mitochondrial dysfunction. In addition, α-synuclein induces the mitochondrial fragmentation on a Drp-1-dependent fashion. Overexpression of the fusion protein Opa-1 prevented both mitochondrial fragmentation and cytotoxicity. On the other hand, cells expressing α-synuclein showed activated autophagy and particularly mitophagy. Employing a genetic strategy we demonstrated that autophagy is triggered in order to protect cells from α-synuclein-induced cell death. Our results clarify the role of Opa-1 and Drp-1 in mitochondrial dynamics and cell survival, a controversial α-synuclein research issue. The findings presented point to the relevance of mitochondrial homeostasis and autophagy in the pathogenesis of PD. Better understanding of the molecular interaction between these processes could give rise to novel therapeutic methods for PD prevention and amelioration. © 2018 Elsevier Inc.

Registro:

Documento: Artículo
Título:Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein
Autor:Martinez, J.H.; Alaimo, A.; Gorojod, R.M.; Porte Alcon, S.; Fuentes, F.; Coluccio Leskow, F.; Kotler, M.L.
Filiación:CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio Interdisciplinario de Dinámica Celular y Nanoherramientas, Argentina
CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina, Buenos Aires, Argentina
Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina
Palabras clave:alpha-synuclein; autophagy; mitochondria; mitochondrial dynamics; mitophagy; Parkinson's Disease; alpha synuclein; dynamin related protein 1; hybrid protein; mitochondrial protein; optic atrophy 1 protein; reactive oxygen metabolite; unclassified drug; alpha synuclein; DNM1L protein, human; guanosine triphosphatase; microtubule associated protein; mitochondrial protein; OPA1 protein, human; SNCA protein, human; Article; autophagy; cell death; cell protection; cell survival; cell viability; controlled study; cytotoxicity; disorders of mitochondrial functions; dopaminergic nerve cell; gene overexpression; human; human cell; in vitro study; mitochondrial dynamics; mitochondrial fragmentation; mitophagy; Parkinson disease; priority journal; SH-SY5Y cell line; wild type; autophagy; dopaminergic nerve cell; genetics; metabolism; mitochondrion; physiology; substantia nigra; tumor cell line; alpha-Synuclein; Autophagy; Cell Line, Tumor; Dopaminergic Neurons; GTP Phosphohydrolases; Humans; Microtubule-Associated Proteins; Mitochondria; Mitochondrial Degradation; Mitochondrial Dynamics; Mitochondrial Proteins; Parkinson Disease; Substantia Nigra
Año:2018
Volumen:88
Página de inicio:107
Página de fin:117
DOI: http://dx.doi.org/10.1016/j.mcn.2018.01.004
Título revista:Molecular and Cellular Neuroscience
Título revista abreviado:Mol. Cell. Neurosci.
ISSN:10447431
CODEN:MOCNE
CAS:alpha synuclein, 154040-18-3; guanosine triphosphatase, 9059-32-9; alpha-Synuclein; DNM1L protein, human; GTP Phosphohydrolases; Microtubule-Associated Proteins; Mitochondrial Proteins; OPA1 protein, human; SNCA protein, human
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10447431_v88_n_p107_Martinez

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Citas:

---------- APA ----------
Martinez, J.H., Alaimo, A., Gorojod, R.M., Porte Alcon, S., Fuentes, F., Coluccio Leskow, F. & Kotler, M.L. (2018) . Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein. Molecular and Cellular Neuroscience, 88, 107-117.
http://dx.doi.org/10.1016/j.mcn.2018.01.004
---------- CHICAGO ----------
Martinez, J.H., Alaimo, A., Gorojod, R.M., Porte Alcon, S., Fuentes, F., Coluccio Leskow, F., et al. "Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein" . Molecular and Cellular Neuroscience 88 (2018) : 107-117.
http://dx.doi.org/10.1016/j.mcn.2018.01.004
---------- MLA ----------
Martinez, J.H., Alaimo, A., Gorojod, R.M., Porte Alcon, S., Fuentes, F., Coluccio Leskow, F., et al. "Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein" . Molecular and Cellular Neuroscience, vol. 88, 2018, pp. 107-117.
http://dx.doi.org/10.1016/j.mcn.2018.01.004
---------- VANCOUVER ----------
Martinez, J.H., Alaimo, A., Gorojod, R.M., Porte Alcon, S., Fuentes, F., Coluccio Leskow, F., et al. Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein. Mol. Cell. Neurosci. 2018;88:107-117.
http://dx.doi.org/10.1016/j.mcn.2018.01.004