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Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death
Open accessAbstract
The p53-inducible protein TIGAR (Tp53-induced Glycolysis and Apoptosis Regulator) functions as a fructose-2,6-bisphosphatase (Fru-2,6-BPase), and through promotion of the pentose phosphate pathway, increases NADPH production to help limit reactive oxygen species (ROS). Here, we show that under hypoxia, a fraction of TIGAR protein relocalized to mitochondria and formed a complex with hexokinase 2 (HK2), resulting in an increase in HK2 activity. Mitochondrial localization of TIGAR depended on mitochondrial HK2 and hypoxia-inducible factor 1 (HIF1α) activity. The ability of TIGAR to function as a Fru-2,6-BPase was independent of HK2 binding and mitochondrial localization, although both of these activities can contribute to the full activity of TIGAR in limiting mitochondrial ROS levels and protecting from cell death.
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Cites
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Tumor suppressors and cell metabolism: a recipe for cancer growth
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Self-citationAZOULAY-ZOHAR, H., ISRAELSON, A., ABU-HAMAD, S., & SHOSHAN-BARMATZ, V. (2004) · Biochemical Journal · doi:10.1042/bj20031465 · Cited by 408
Cited by
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931
Ferroptosis as a p53-mediated activity during tumour suppression
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Sugar for the brain: the role of glucose in physiological and pathological brain function
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The return of metabolism: biochemistry and physiology of the pentose phosphate pathway
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Self-citationP53 in survival, death and metabolic health: a lifeguard with a licence to kill.
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Metadata
- Authors
- Cheung, E. C., Ludwig, R. L., & Vousden, K. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-11-26
- Volume
- 109
- Issue
- 50
- Pages
- 20491-20496
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2051173337
- Cited by
- 244
- References
- 6
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- green
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- Cheung, E. C., Ludwig, R. L., & Vousden, K. H. (2012). Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1206530109
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