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Metabolic studies of a patient harbouring a novel S487L mutation in the catalytic subunit of AMPK.
Arita, Juliana Harumi; Barros, Mário H; Ravagnani, Felipe Gustavo; Ziosi, Marcello; Sanches, Lívia Rentas; Picosse, Fabíola Rosa; Lopes, Tania Oliveira; de Carvalho Aguiar, Patrícia; Macabelli, Carolina Habermann; Chiaratti, Marcos R; Pedroso, José Luiz; Quinzii, Catarina M; Barsottini, Orlando Graziani Póvoas; Ferreiro-Barros, Claudia Cristina.
Afiliación
  • Arita JH; Setor de Neurologia Infantil, Departamento de Neurologia, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
  • Barros MH; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
  • Ravagnani FG; Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
  • Ziosi M; Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • Sanches LR; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
  • Picosse FR; Departamento de Dermatologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Lopes TO; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
  • de Carvalho Aguiar P; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; Departmento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Macabelli CH; Departmento de Genética e Evolução, Universidade Federal de São Carlos, UFSCar, São Paulo, SP, Brazil.
  • Chiaratti MR; Departmento de Genética e Evolução, Universidade Federal de São Carlos, UFSCar, São Paulo, SP, Brazil.
  • Pedroso JL; Departmento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Quinzii CM; Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • Barsottini OGP; Departmento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Ferreiro-Barros CC; Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: claudia.barros@fm.usp.br.
Biochim Biophys Acta Mol Basis Dis ; 1864(5 Pt A): 1896-1903, 2018 May.
Article en En | MEDLINE | ID: mdl-29526819
AMP-activated protein kinase (AMPK) regulates many different metabolic pathways in eukaryote cells including mitochondria biogenesis and energy homeostasis. Here we identify a patient with hypotonia, weakness, delayed milestones and neurological impairment since birth harbouring a novel homozygous mutation in the AMPK catalytic α-subunit 1, encoded by the PRKAA1 gene. The homozygous mutation p.S487L in isoform 1 present in the patient is in a cryptic residue for AMPK activity. In the present study, we performed the characterization of mitochondrial respiratory properties of the patient, in comparison to healthy controls, through the culture of skin fibroblasts in order to understand some of the cellular consequences of the PRKAA1 mutation. In these assays, mitochondrial respiratory complex I showed lower activity, which was followed by a decrement in the mtDNA copy number, which is a probable consequence of the lower expression of PGC-1α and PRKAA1 itself as measured in our quantitative PCRs experiments. Confirming the effect of the patient mutation in respiration, transfection of patient fibroblasts with wild type PRKAA1 partially restore complex I level. The preliminary clinic evaluations of the patient suggested a metabolic defect related to the mitochondrial respiratory function, therefore treatment with CoQ10 supplementation dose started four years ago and a clear improvement in motor skills and strength has been achieved with this treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consumo de Oxígeno / Mutación Missense / Proteínas Quinasas Activadas por AMP / Fibroblastos / Homocigoto / Mitocondrias Tipo de estudio: Prognostic_studies Límite: Child, preschool / Humans / Male Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2018 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consumo de Oxígeno / Mutación Missense / Proteínas Quinasas Activadas por AMP / Fibroblastos / Homocigoto / Mitocondrias Tipo de estudio: Prognostic_studies Límite: Child, preschool / Humans / Male Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2018 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos