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.
Keywords: Energy metabolism, glycolysis, hexokinase, lactate, neurons, VDAC.
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