Role of Hexokinase and VDAC in Neurological Disorders

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 consequ...

Full description

Saved in:
Bibliographic Details
Published inCurrent molecular pharmacology Vol. 9; no. 4; p. 320
Main Authors Rosa, José César, César, Marcelo de Cerqueira
Format Journal Article
LanguageEnglish
Published United Arab Emirates 01.11.2016
Subjects
Animals
Brain - metabolism
Brain - pathology
Hexokinase - metabolism
Humans
Mitochondria - metabolism
Nervous System Diseases - metabolism
Neurons - metabolism
Neurons - pathology
Voltage-Dependent Anion Channels - metabolism
Online AccessGet more information

Cover

More Information
Summary: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.
ISSN:1874-4702
DOI:10.2174/1874467209666160112123036