PMID- 29119535 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20191210 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 55 IP - 7 DP - 2018 Jul TI - Mitochondria-Bound Hexokinase (mt-HK) Activity Differ in Cortical and Hypothalamic Synaptosomes: Differential Role of mt-HK in H(2)O(2) Depuration. PG - 5889-5900 LID - 10.1007/s12035-017-0807-9 [doi] AB - Glucose and oxygen are vital for the brain, as these molecules provide energy and metabolic intermediates that are necessary for cell function. The glycolysis pathway and mitochondria play a pivotal role in cell energy metabolism, which is closely related to reactive oxygen species (ROS) production. Hexokinase (HK) is a key enzyme involved in glucose metabolism that modulates the level of brain mitochondrial ROS by recycling ADP for oxidative phosphorylation (OxPhos). Here, we hypothesize that the control of mitochondrial metabolism by hexokinase differs in distinct areas of the brain, such as the cortex and hypothalamus, in which ROS might function as signaling molecules. Thus, we investigated mitochondrial metabolism of synaptosomes derived from both brain regions. Cortical synaptosomes (CSy) show a predominance of glutamatergic synapses, while in the hypothalamic synaptosomes (HSy), the GABAergic synapses predominate. Significant differences of oxygen consumption and ROS production were related to higher mitochondrial complex II activity (succinate dehydrogenase-SDH) in CSy rather than to mitochondrial number. Mitochondrial HK (mt-HK) activity was higher in CSy than in HSy regardless the substrate added. Mitochondrial O(2) consumption related to mt-HK activation by 2-deoxyglucose was also higher in CSy. In the presence of substrate for complex II, the activation of synaptosomal mt-HK promoted depuration of ROS in both HSy and CSy, while ROS depuration did not occur in HSy when substrate for complex I was used. The impact of the mt-HK inhibition by glucose-6-phosphate (G6P) was the same in synaptosomes from both areas. Together, the differences found between CSy and HSy indicate specific roles of mt-HK and SDH on the metabolism of each brain region, what probably depends on the main metabolic route that is used by the neurons. FAU - Cavalcanti-de-Albuquerque, Joao Paulo AU - Cavalcanti-de-Albuquerque JP AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. AD - Laboratorio de Bioenergetica e Fisiologia Mitocondrial, UFRJ, Av. Carlos Chagas Filho, 373. Bloco D-Sala Dss0-13, Rio de Janeiro, Ilha do Fundao, CEP 21941-902, Brazil. FAU - de Souza Ferreira, Eduardo AU - de Souza Ferreira E AD - Institute of Medical Biochemistry Leopoldo De Meis, Center of Health Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. AD - Laboratorio de Bioenergetica e Fisiologia Mitocondrial, UFRJ, Av. Carlos Chagas Filho, 373. Bloco D-Sala Dss0-13, Rio de Janeiro, Ilha do Fundao, CEP 21941-902, Brazil. FAU - de Carvalho, Denise Pires AU - de Carvalho DP AD - Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Galina, Antonio AU - Galina A AD - Institute of Medical Biochemistry Leopoldo De Meis, Center of Health Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. galina@bioqmed.ufrj.br. AD - Laboratorio de Bioenergetica e Fisiologia Mitocondrial, UFRJ, Av. Carlos Chagas Filho, 373. Bloco D-Sala Dss0-13, Rio de Janeiro, Ilha do Fundao, CEP 21941-902, Brazil. galina@bioqmed.ufrj.br. LA - eng PT - Journal Article DEP - 20171108 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Reactive Oxygen Species) RN - 56-73-5 (Glucose-6-Phosphate) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.3.5.1 (Electron Transport Complex II) RN - EC 2.7.1.1 (Hexokinase) RN - EC 7.1.1.2 (Electron Transport Complex I) SB - IM MH - Animals MH - Cerebral Cortex/*enzymology MH - Electron Transport Complex I/metabolism MH - Electron Transport Complex II/metabolism MH - Glucose-6-Phosphate/pharmacology MH - Hexokinase/*metabolism MH - Hydrogen Peroxide/*metabolism MH - Hypothalamus/*enzymology MH - Male MH - Mitochondria/drug effects/*metabolism MH - Oxygen Consumption/drug effects MH - Rats, Wistar MH - Reactive Oxygen Species/metabolism MH - Substrate Specificity/drug effects MH - Synaptosomes/drug effects/*enzymology OTO - NOTNLM OT - Bioenergetics OT - Brain OT - Hexokinase OT - Mitochondria OT - Succinate dehydrogenase OT - Synaptosome EDAT- 2017/11/10 06:00 MHDA- 2019/02/05 06:00 CRDT- 2017/11/10 06:00 PHST- 2017/06/01 00:00 [received] PHST- 2017/10/18 00:00 [accepted] PHST- 2017/11/10 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2017/11/10 06:00 [entrez] AID - 10.1007/s12035-017-0807-9 [pii] AID - 10.1007/s12035-017-0807-9 [doi] PST - ppublish SO - Mol Neurobiol. 2018 Jul;55(7):5889-5900. doi: 10.1007/s12035-017-0807-9. Epub 2017 Nov 8.