Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/103965
Title: MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile
Authors: Jacinto, Sandra
Guerreiro, Patrícia
Oliveira, Rita Machado de
Oliveira, Teresa Cunha 
Santos, Maria João 
Grazina, Manuela 
Rego, A. Cristina 
Outeiro, Tiago F. 
Keywords: Mpv17 mutations; mitochondrial depletion syndrome; mitochondrial dysfunction; protein mislocation; neurode generation
Issue Date: 2021
Publisher: Frontiers Media S.A.
Project: Fundação Calouste Gulbenkian 
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2067/1- 390729940) 
CENTRO-01-0145-FEDER- 000012- HealthyAging2020 
POCI-010145-FEDER-007440) 
POCI-01-145-FEDER-29297 
UID/NEU/04539/2019 (Strategic Plan CNC.IBILI) 
Serial title, monograph or event: Frontiers in Cellular Neuroscience
Volume: 15
Abstract: 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.
URI: https://hdl.handle.net/10316/103965
ISSN: 1662-5102
DOI: 10.3389/fncel.2021.641264
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais

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