MPV17 mutations are associated with a quiescent energetic metabolic profile

Detalhes bibliográficos
Autor(a) principal: Jacinto, Sandra
Data de Publicação: 2021
Outros Autores: Guerreiro, Patrícia, de Oliveira, Rita Machado, Cunha-Oliveira, Teresa, Santos, Maria João, Grazina, Manuela, Rego, Ana Cristina, Outeiro, Tiago
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/50228
Resumo: © 2021 Jacinto, Guerreiro, de Oliveira, Cunha-Oliveira, Santos, Grazina, Rego and Outeiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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spelling MPV17 mutations are associated with a quiescent energetic metabolic profileMpv17 mutationsMitochondrial depletion syndromeMitochondrial dysfunctionNeurode generationProtein mislocation© 2021 Jacinto, Guerreiro, de Oliveira, Cunha-Oliveira, Santos, Grazina, Rego and Outeiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be important in the maintenance of mitochondrial membrane potential (ΔΨm). To obtain more information about the role of MPV17 in human disease, we investigated the effect of MPV17 knockdown and of selected known MPV17 mutations associated with MPV17 disease in vitro. We used different approaches in order to evaluate the cellular consequences of MPV17 deficiency. We found that lower levels of MPV17 were associated with impaired mitochondrial respiration and with a quiescent energetic metabolic profile. All the mutations studied destabilized the protein, resulting in reduced protein levels. We also demonstrated that different mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of ΔΨm, and mislocalization of MPV17 protein. Our study provides novel insight into the molecular effects of MPV17 mutations and opens novel possibilities for testing therapeutic strategies for a devastating group of disorders.SJ was funded by Fundação Calouste Gulbenkian. TO was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC 2067/1- 390729940). AR and TC-O were funded by Fundação para a Ciência e a Tecnologia and European Regional Development Fund (CENTRO-01-0145-FEDER-000012- HealthyAging2020), (POCI-010145-FEDER-007440), and (POCI-01-145-FEDER-29297). MS and MG were funded by UID/NEU/04539/2019 (Strategic Plan CNC.IBILI).FrontiersRepositório da Universidade de LisboaJacinto, SandraGuerreiro, Patríciade Oliveira, Rita MachadoCunha-Oliveira, TeresaSantos, Maria JoãoGrazina, ManuelaRego, Ana CristinaOuteiro, Tiago2021-11-30T15:33:20Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50228engFront Cell Neurosci. 2021 Mar 17;15:64126410.3389/fncel.2021.6412641662-5102info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:54:12Zoai:repositorio.ul.pt:10451/50228Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:38.279894Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv MPV17 mutations are associated with a quiescent energetic metabolic profile
title MPV17 mutations are associated with a quiescent energetic metabolic profile
spellingShingle MPV17 mutations are associated with a quiescent energetic metabolic profile
Jacinto, Sandra
Mpv17 mutations
Mitochondrial depletion syndrome
Mitochondrial dysfunction
Neurode generation
Protein mislocation
title_short MPV17 mutations are associated with a quiescent energetic metabolic profile
title_full MPV17 mutations are associated with a quiescent energetic metabolic profile
title_fullStr MPV17 mutations are associated with a quiescent energetic metabolic profile
title_full_unstemmed MPV17 mutations are associated with a quiescent energetic metabolic profile
title_sort MPV17 mutations are associated with a quiescent energetic metabolic profile
author Jacinto, Sandra
author_facet Jacinto, Sandra
Guerreiro, Patrícia
de Oliveira, Rita Machado
Cunha-Oliveira, Teresa
Santos, Maria João
Grazina, Manuela
Rego, Ana Cristina
Outeiro, Tiago
author_role author
author2 Guerreiro, Patrícia
de Oliveira, Rita Machado
Cunha-Oliveira, Teresa
Santos, Maria João
Grazina, Manuela
Rego, Ana Cristina
Outeiro, Tiago
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Jacinto, Sandra
Guerreiro, Patrícia
de Oliveira, Rita Machado
Cunha-Oliveira, Teresa
Santos, Maria João
Grazina, Manuela
Rego, Ana Cristina
Outeiro, Tiago
dc.subject.por.fl_str_mv Mpv17 mutations
Mitochondrial depletion syndrome
Mitochondrial dysfunction
Neurode generation
Protein mislocation
topic Mpv17 mutations
Mitochondrial depletion syndrome
Mitochondrial dysfunction
Neurode generation
Protein mislocation
description © 2021 Jacinto, Guerreiro, de Oliveira, Cunha-Oliveira, Santos, Grazina, Rego and Outeiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-30T15:33:20Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50228
url http://hdl.handle.net/10451/50228
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Cell Neurosci. 2021 Mar 17;15:641264
10.3389/fncel.2021.641264
1662-5102
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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