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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Agustina Alaimo, Roxana M Gorojod, Juan Beauquis, Manuel J Muñoz, Flavia Saravia, Mónica L Kotler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b8b596b35b64ab7afd21e5e8a6acc72
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4b8b596b35b64ab7afd21e5e8a6acc72
record_format	dspace
spelling	oai:doaj.org-article:4b8b596b35b64ab7afd21e5e8a6acc722021-11-18T08:28:07ZDeregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.1932-620310.1371/journal.pone.0091848https://doaj.org/article/4b8b596b35b64ab7afd21e5e8a6acc722014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24632637/?tool=EBIhttps://doaj.org/toc/1932-6203Mitochondria 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.Agustina AlaimoRoxana M GorojodJuan BeauquisManuel J MuñozFlavia SaraviaMónica L KotlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91848 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agustina Alaimo Roxana M Gorojod Juan Beauquis Manuel J Muñoz Flavia Saravia Mónica L Kotler Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.
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.
format	article
author	Agustina Alaimo Roxana M Gorojod Juan Beauquis Manuel J Muñoz Flavia Saravia Mónica L Kotler
author_facet	Agustina Alaimo Roxana M Gorojod Juan Beauquis Manuel J Muñoz Flavia Saravia Mónica L Kotler
author_sort	Agustina Alaimo
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.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4b8b596b35b64ab7afd21e5e8a6acc72
work_keys_str_mv	AT agustinaalaimo deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT roxanamgorojod deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT juanbeauquis deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT manueljmunoz deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT flaviasaravia deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis AT monicalkotler deregulationofmitochondriashapingproteinsopa1anddrp1inmanganeseinducedapoptosis
_version_	1718421736942206976

Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.

Ejemplares similares