Metabolic studies of a patient harbouring a novel S487L mutation in the catalytic subunit of AMPK

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dc.citation.issue5
dc.citation.volumev. 1864
dc.contributor.authorArita, Juliana Harumi [UNIFESP]
dc.contributor.authorBarros, Mario H.
dc.contributor.authorRavagnani, Felipe Gustavo
dc.contributor.authorZiosi, Marcello
dc.contributor.authorSanches, Livia Rentas
dc.contributor.authorPicosse, Fabíola Rosa [UNIFESP]
dc.contributor.authorLopes, Tania Oliveira
dc.contributor.authorAguiar, Patricia de Carvalho [UNIFESP]
dc.contributor.authorMacabelli, Carolina Habermann
dc.contributor.authorChiaratti, Marcos R.
dc.contributor.authorPedroso, Jose Luiz [UNIFESP]
dc.contributor.authorQuinzii, Catarina M.
dc.contributor.authorBarsottini, Orlando Graziani Povoas [UNIFESP]
dc.contributor.authorFerreiro-Barros, Claudia Cristina [UNIFESP]
dc.coverageAmsterdam
dc.date.accessioned2020-07-20T16:30:54Z
dc.date.available2020-07-20T16:30:54Z
dc.date.issued2018
dc.description.abstractAMP-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 alpha-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-1 alpha 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.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Neurol, Setor Neurol Infantil, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Ciencias Biomed, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Quim, Sao Paulo, SP, Brazil
dc.description.affiliationHosp Israelita Albert Einstein, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Dermatol, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Neurol & Neurocirurgia, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Carlos, UFSCar, Dept Genet & Evolucao, Sao Paulo, SP, Brazil
dc.description.affiliationColumbia Univ, Dept Neurol, Med Ctr, New York, NY USA
dc.description.affiliationUniv Sao Paulo, Fac Med, Dept Clin Med, Av Dr Arnaldo 455, BR-01246000 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Neurol, Setor Neurol Infantil, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Dermatol, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Neurol & Neurocirurgia, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2010/51924-0
dc.description.sponsorshipIDFAPESP: 2011/07366-5
dc.description.sponsorshipIDFAPESP: 2013/07937-8
dc.description.sponsorshipIDFAPESP: 2015/23549-3
dc.format.extent1896-1903
dc.identifierhttp://dx.doi.org/10.1016/j.bbadis.2018.03.011
dc.identifier.citationBiochimica Et Biophysica Acta-Molecular Basis Of Disease. Amsterdam, v. 1864, n. 5, p. 1896-1903, 2018.
dc.identifier.doi10.1016/j.bbadis.2018.03.011
dc.identifier.issn0925-4439
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55580
dc.identifier.wosWOS:000430883100032
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.relation.ispartofBiochimica Et Biophysica Acta-Molecular Basis Of Disease
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAMPKen
dc.subjectPRKAA1en
dc.subjectNeurological impairmenten
dc.subjectMitochondriaen
dc.subjectOxidative phosphorylationen
dc.subjectMitochondrial diseasesen
dc.titleMetabolic studies of a patient harbouring a novel S487L mutation in the catalytic subunit of AMPKen
dc.typeinfo:eu-repo/semantics/article
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