VDAC1 serves as a mitochondrial binding site for hexokinase in oxidative muscles.
Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are the main pathway for metabolites across the mitochondrial outer membrane and may serve as binding sites for kinases, including hexokinase. We determined that mitochondria-bound hexokinase activity is significantly reduced in oxidative muscles (heart and soleus) in vdac1(-/-) mice. The activity data were supported by western blot analysis using HK2 specific antibody. To gain more insight into the physiologic mean of the results with the activity data, VDAC deficient mice were subjected to glucose tolerance testing and exercise-induced stress, each of which involves tissue glucose uptake via different mechanisms. vdac1(-/-) mice exhibit impaired glucose tolerance whereas vdac3(-/-) mice have normal glucose tolerance and exercise capacity. Mice lacking both VDAC1 and VDAC3 (vdac1(-/-)/vdac3(-/-)) have reduced exercise capacity together with impaired glucose tolerance. Therefore, we demonstrated a link between VDAC1 mediated mitochondria-bound hexokinase activity and the capacity for glucose clearance.
Anflous-Pharayra
Keltoum
K
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. ayapharayra@yahoo.com
Cai
Zong-Jin
ZJ
Craigen
William J
WJ
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D005260:Female; D005951:Glucose Tolerance Test; D006593:Hexokinase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000172:deficiency; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000172:deficiency / Q000502:physiology*; D050994:Voltage-Dependent Anion Channels / Q000172:deficiency
D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C494763:Vdac1 protein, mouse; C480078:Vdac3 protein, mouse; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1; D006593:Hexokinase