GIST Scholar
College of Life Sciences and Medical Engineering
Department of Life Sciences
1. Journal Articles
A Lactate-Induced Response to Hypoxia
- Type
- Article
- Citation
- CELL, v.161, no.3, pp.595 - 609
- Issued Date
- 2015-04
- Abstract
- Organisms must be able to respond to low oxygen in a number of homeostatic and pathological contexts. Regulation of hypoxic responses via the hypoxia-inducible factor (HIF) is well established, but evidence indicates that other, HIF-independent mechanisms are also involved. Here, we report a hypoxic response that depends on the accumulation of lactate, a metabolite whose production increases in hypoxic conditions. We find that the NDRG3 protein is degraded in a PHD2/VHL-dependent manner in normoxia but is protected from destruction by binding to lactate that accumulates under hypoxia. The stabilized NDRG3 protein binds c-Raf to mediate hypoxia-induced activation of Raf-ERK pathway, promoting angiogenesis and cell growth. Inhibiting cellular lactate production abolishes the NDRG3-mediated hypoxia responses. Our study, therefore, elucidates the molecular basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases.
- Publisher
- CELL PRESS
- ISSN
- 0092-8674
- Appears in Collections:
- Department of Life Sciences > 1. Journal Articles
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