Cellular adaptation to hypoxia through hypoxia inducible factors and beyond

缺氧(环境) 生物能学 细胞适应 线粒体 缺氧诱导因子 活性氧 糖酵解 细胞生物学 氧化应激 新陈代谢 血管生成 生物 平衡 生物化学 化学 氧气 基因 癌症研究 有机化学
作者
Pearl Lee,Navdeep S. Chandel,M. Celeste Simon
出处
期刊:Nature Reviews Molecular Cell Biology [Springer Nature]
卷期号:21 (5): 268-283 被引量:754
标识
DOI:10.1038/s41580-020-0227-y
摘要

Molecular oxygen (O2) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP-consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best-studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine-tuning the responses to hypoxic stress. The transcriptional response to hypoxia and the role of hypoxia inducible factors have been extensively studied. Yet, hypoxic cells also adapt to hypoxia by modulating protein synthesis, metabolism and nutrient uptake. Understanding these processes could shed light on pathologies associated with hypoxia, including cardiovascular diseases and cancer, and disease mechanisms, such as inflammation and wound repair.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
1秒前
2秒前
许飞飞飞完成签到,获得积分10
4秒前
彭于晏应助房山芙采纳,获得10
4秒前
懒YY捉小J发布了新的文献求助10
5秒前
李健的粉丝团团长应助DKN采纳,获得10
6秒前
6秒前
6秒前
6秒前
淡然仰完成签到,获得积分10
7秒前
7秒前
王不留行发布了新的文献求助10
8秒前
嘻嘻哈哈完成签到,获得积分10
8秒前
斯文的樱发布了新的文献求助10
10秒前
Blummer发布了新的文献求助20
11秒前
11秒前
12秒前
STR发布了新的文献求助10
12秒前
轻吟发布了新的文献求助10
12秒前
Aurora.H完成签到,获得积分10
13秒前
guard发布了新的文献求助10
14秒前
14秒前
陶珊发布了新的文献求助10
15秒前
moiumuio完成签到,获得积分10
16秒前
17秒前
小张完成签到,获得积分10
17秒前
18秒前
18秒前
哎嘤斯坦发布了新的文献求助10
19秒前
Herry-Jeremy完成签到,获得积分10
20秒前
20秒前
凉兮完成签到,获得积分10
22秒前
如意的惮发布了新的文献求助10
22秒前
欧维发布了新的文献求助10
22秒前
科目三应助老实人品牌采纳,获得30
22秒前
berg发布了新的文献求助10
24秒前
24秒前
从容芮应助哎嘤斯坦采纳,获得10
25秒前
科研通AI2S应助syf采纳,获得10
25秒前
高分求助中
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Foreign Policy of the French Second Empire: A Bibliography 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
XAFS for Everyone 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3145328
求助须知:如何正确求助?哪些是违规求助? 2796792
关于积分的说明 7821187
捐赠科研通 2453031
什么是DOI,文献DOI怎么找? 1305409
科研通“疑难数据库(出版商)”最低求助积分说明 627487
版权声明 601464