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 F.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/116086
Resumo: Funding: 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-FEDER000012- 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).
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spelling MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profilemitochondrial depletion syndromemitochondrial dysfunctionMpv17 mutationsneurode generationprotein mislocationCellular and Molecular NeuroscienceSDG 3 - Good Health and Well-beingFunding: 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-FEDER000012- 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).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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNJacinto, SandraGuerreiro, Patríciade Oliveira, Rita MachadoCunha-Oliveira, TeresaSantos, Maria JoãoGrazina, ManuelaRego, Ana CristinaOuteiro, Tiago F.2021-04-23T22:57:14Z2021-03-172021-03-17T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/116086eng1662-5102PURE: 29165635https://doi.org/10.3389/fncel.2021.641264info: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:RCAAP2024-03-11T04:58:38Zoai:run.unl.pt:10362/116086Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:42:58.648291Repositório 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
mitochondrial depletion syndrome
mitochondrial dysfunction
Mpv17 mutations
neurode generation
protein mislocation
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
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 F.
author_role author
author2 Guerreiro, Patrícia
de Oliveira, Rita Machado
Cunha-Oliveira, Teresa
Santos, Maria João
Grazina, Manuela
Rego, Ana Cristina
Outeiro, Tiago F.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
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 F.
dc.subject.por.fl_str_mv mitochondrial depletion syndrome
mitochondrial dysfunction
Mpv17 mutations
neurode generation
protein mislocation
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
topic mitochondrial depletion syndrome
mitochondrial dysfunction
Mpv17 mutations
neurode generation
protein mislocation
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
description Funding: 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-FEDER000012- 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).
publishDate 2021
dc.date.none.fl_str_mv 2021-04-23T22:57:14Z
2021-03-17
2021-03-17T00:00:00Z
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/10362/116086
url http://hdl.handle.net/10362/116086
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1662-5102
PURE: 29165635
https://doi.org/10.3389/fncel.2021.641264
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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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
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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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