MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
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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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 |
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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 |
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1662-5102 PURE: 29165635 https://doi.org/10.3389/fncel.2021.641264 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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