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Mitochondria-coupled glucose phosphorylation develops after birth to modulate H2 O2 release and calcium handling in rat brain.
de-Souza-Ferreira, Eduardo; Rios-Neto, Izac Miranda; Martins, Eduarda Lopes; Galina, Antonio.
Afiliação
  • de-Souza-Ferreira E; Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Rios-Neto IM; Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Martins EL; Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Galina A; Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
J Neurochem ; 149(5): 624-640, 2019 06.
Article em En | MEDLINE | ID: mdl-31001830
The adult brain is a high-glucose and oxygen-dependent organ, with an extremely organized network of cells and large energy-consuming synapses. To reach this level of organization, early stages in development must include an efficient control of cellular events and regulation of intracellular signaling molecules and ions such as hydrogen peroxide (H2 O2 ) and calcium (Ca2+ ), but in cerebral tissue, these mechanisms of regulation are still poorly understood. Hexokinase (HK) is the first enzyme in the metabolism of glucose and, when bound to mitochondria (mtHK), it has been proposed to have a role in modulation of mitochondrial H2 O2  generation and Ca2+ handling. Here, we have investigated how mtHK modulates these signals in the mitochondrial context during postnatal development of the mouse brain. Using high-resolution respirometry, western blot analysis, spectrometry and resorufin, and Calcium Green fluorescence assays with brain mitochondria purified postnatally from day 1 to day 60, we demonstrate that brain HK increases its coupling to mitochondria and to oxidative phosphorylation to induce a cycle of ADP entry/ATP exit of the mitochondrial matrix that leads to efficient control over H2 O2 generation and Ca2+ uptake during development until reaching plateau at day 21. This contrasts sharply with the antioxidant enzymes, which do not increase as mitochondrial H2 O2 generation escalates. These results suggest that, as its use of glucose increases, the brain couples HK to mitochondria to improve glucose metabolism, redox balance and Ca2+ signaling during development, positioning mitochondria-bound hexokinase as a hub for intracellular signaling control.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Cálcio / Glucose / Hexoquinase / Peróxido de Hidrogênio / Mitocôndrias Limite: Animals Idioma: En Revista: J Neurochem Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Cálcio / Glucose / Hexoquinase / Peróxido de Hidrogênio / Mitocôndrias Limite: Animals Idioma: En Revista: J Neurochem Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido