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.
Pubmed ID: 31001830 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets VDAC1
View all literature mentionsThis monoclonal targets Hexokinase I
View all literature mentionsThis polyclonal targets Beta-Tubulin
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsA complete graphing and data analysis software package that provides a suite of features catering to the needs of scientists and engineers. Main features: * Drag-and-drop import of data and images * Save import settings to a worksheet or external files for repeated use * Use saved settings to re-import files with a single click * Post-process imported data * Import Wizard with visual feedback * Handle non-standard files by programming
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsRattus norvegicus with name WI from RGD.
View all literature mentionsA complete graphing and data analysis software package that provides a suite of features catering to the needs of scientists and engineers. Main features: * Drag-and-drop import of data and images * Save import settings to a worksheet or external files for repeated use * Use saved settings to re-import files with a single click * Post-process imported data * Import Wizard with visual feedback * Handle non-standard files by programming
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentions