期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
卷 1767, 期 2, 页码 136-142出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbabio.2006.11.013
关键词
mitochondrial outer membrane; muscle; porin; hexokinase; glucose clearance; exercise capacity
资金
- NIGMS NIH HHS [R01 GM55713] Funding Source: Medline
- NINDS NIH HHS [R01 NS42319] Funding Source: Medline
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. (c) 2006 Elsevier B.V. All rights reserved.
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