Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis
Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence corre...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v9_n3_p_Alaimo http://hdl.handle.net/20.500.12110/paper_19326203_v9_n3_p_Alaimo |
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paper:paper_19326203_v9_n3_p_Alaimo2023-06-08T16:31:21Z Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis Alaimo, Agustina Muñoz, Manuel Javier Kotler, Mónica Lidia manganese mitochondrial protein protein Drp 1 protein Opa 1 small interfering RNA unclassified drug animal cell animal experiment animal model animal tissue apoptosis article astrocyte basal ganglion bioaccumulation brain region cell disruption cellular distribution controlled study cytosol cytotoxicity disorders of mitochondrial functions male molecular dynamics nonhuman parkinsonism protein analysis protein expression protein function protein localization protein transport rat toxicity testing upregulation Animals Apoptosis Cell Line, Tumor Cyclosporine Dynamins Gene Expression Regulation GTP Phosphohydrolases Intracellular Space Male Manganese Membrane Potential, Mitochondrial Mitochondria Neostriatum Protein Transport Rats Rats, Sprague-Dawley Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may provide new therapeutic tools for the treatment of Manganism and other neurodegenerative diseases. © 2014 Alaimo et al. Fil:Alaimo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Muñoz, M.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kotler, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v9_n3_p_Alaimo http://hdl.handle.net/20.500.12110/paper_19326203_v9_n3_p_Alaimo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
manganese mitochondrial protein protein Drp 1 protein Opa 1 small interfering RNA unclassified drug animal cell animal experiment animal model animal tissue apoptosis article astrocyte basal ganglion bioaccumulation brain region cell disruption cellular distribution controlled study cytosol cytotoxicity disorders of mitochondrial functions male molecular dynamics nonhuman parkinsonism protein analysis protein expression protein function protein localization protein transport rat toxicity testing upregulation Animals Apoptosis Cell Line, Tumor Cyclosporine Dynamins Gene Expression Regulation GTP Phosphohydrolases Intracellular Space Male Manganese Membrane Potential, Mitochondrial Mitochondria Neostriatum Protein Transport Rats Rats, Sprague-Dawley |
| spellingShingle |
manganese mitochondrial protein protein Drp 1 protein Opa 1 small interfering RNA unclassified drug animal cell animal experiment animal model animal tissue apoptosis article astrocyte basal ganglion bioaccumulation brain region cell disruption cellular distribution controlled study cytosol cytotoxicity disorders of mitochondrial functions male molecular dynamics nonhuman parkinsonism protein analysis protein expression protein function protein localization protein transport rat toxicity testing upregulation Animals Apoptosis Cell Line, Tumor Cyclosporine Dynamins Gene Expression Regulation GTP Phosphohydrolases Intracellular Space Male Manganese Membrane Potential, Mitochondrial Mitochondria Neostriatum Protein Transport Rats Rats, Sprague-Dawley Alaimo, Agustina Muñoz, Manuel Javier Kotler, Mónica Lidia Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis |
| topic_facet |
manganese mitochondrial protein protein Drp 1 protein Opa 1 small interfering RNA unclassified drug animal cell animal experiment animal model animal tissue apoptosis article astrocyte basal ganglion bioaccumulation brain region cell disruption cellular distribution controlled study cytosol cytotoxicity disorders of mitochondrial functions male molecular dynamics nonhuman parkinsonism protein analysis protein expression protein function protein localization protein transport rat toxicity testing upregulation Animals Apoptosis Cell Line, Tumor Cyclosporine Dynamins Gene Expression Regulation GTP Phosphohydrolases Intracellular Space Male Manganese Membrane Potential, Mitochondrial Mitochondria Neostriatum Protein Transport Rats Rats, Sprague-Dawley |
| description |
Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may provide new therapeutic tools for the treatment of Manganism and other neurodegenerative diseases. © 2014 Alaimo et al. |
| author |
Alaimo, Agustina Muñoz, Manuel Javier Kotler, Mónica Lidia |
| author_facet |
Alaimo, Agustina Muñoz, Manuel Javier Kotler, Mónica Lidia |
| author_sort |
Alaimo, Agustina |
| title |
Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis |
| title_short |
Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis |
| title_full |
Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis |
| title_fullStr |
Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis |
| title_full_unstemmed |
Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis |
| title_sort |
deregulation of mitochondria-shaping proteins opa-1 and drp-1 in manganese-induced apoptosis |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v9_n3_p_Alaimo http://hdl.handle.net/20.500.12110/paper_19326203_v9_n3_p_Alaimo |
| work_keys_str_mv |
AT alaimoagustina deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT munozmanueljavier deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT kotlermonicalidia deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis |
| _version_ |
1768545622608052224 |