Role of Hexokinase and VDAC in Neurological Disorders

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Author(s):	Rosa, Jose Cesar ; Cesar, Marcelo de Cerqueira Total Authors: 2
Document type:	Review article
Source:	CURRENT MOLECULAR PHARMACOLOGY; v. 9, n. 4, p. 320-331, 2016.
Web of Science Citations:	7
Abstract
Several neurological diseases such as bipolar disorders and schizophrenia are linked to impaired brain energy metabolism. A key feature of brain bioenergetics is hexokinase (HK) binding to the outer mitochondrial membrane through the voltage dependent anion channel (VDAC). This has metabolic consequences, with phosphorylation of glucose by mitochondrially bound hexokinase being closely coupled to production of substrate ATP by intramitochondrial oxidative phosphorylation. Additionally, binding of HK to mitochondria inhibits Bax-induced cytochrome c release and apoptosis. Moreover VDAC1 expression level is elevated in cerebellum of patients with Down's syndrome, while in Alzheimer's disease, VDAC1 levels are decreased in frontal cortex and VDAC2 elevated in temporal cortex. Thus, understanding the roles of VDAC and HK, either separate or interacting in brain, provides new opportunities and challenges to elucidate pathophysiological mechanisms for future therapeutic strategies. (AU)

FAPESP's process:	10/05560-6 - Interactomic analysis of hexokinase-VDAC-ANT complex in rat, bovine and chicken neuronal cells
Grantee:	Marcelo de Cerqueira César
Support Opportunities:	Regular Research Grants