氧气浓度可能调控疾病严重程度
2020-04-13   阅读:328   来源:细胞

美国哈佛医学院Vamsi K. Mootha研究组提出了高氧或低氧细胞适应性的遗传筛查突出线粒体和脂质代谢作用。202046日出版的《细胞》杂志发表了这一成果。

他们以21%、5%和1%的氧气进行全基因组CRISPR生长筛查,以系统性地鉴定出在高氧气(213个基因)或低氧气(109个基因)中具有相对适应性缺陷的基因敲除,大多数与缺氧诱导因子(HIF)或活性氧(ROS)无关。

许多线粒体途径基因的敲除被认为是必不可少的,包括复杂的IFe-S生物合成中的酶,在低氧条件下生长相对良好,因此受到缺氧的缓冲。相反,在某些细胞类型中,脂质生物合成和过氧化物酶体基因的敲除仅在低氧条件下才导致适应性缺陷。他们的结果提出可能由氧气调节其严重程度的遗传疾病,并将数百个基因与氧气稳态联系在一起。

研究人员表示,人类细胞能够感知并适应氧气水平的变化。历史上,该领域的许多研究都集中在HIF信号和ROS上。

附:英文原文

Title: Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism

Author: Isha H. Jain, Sarah E. Calvo, Andrew L. Markhard, Owen S. Skinner, Tsz-Leung To, Tslil Ast, Vamsi K. Mootha

Issue&Volume: 2020-04-06

Abstract: Human cells are able to sense and adapt to variations in oxygen levels. Historically,much research in this field has focused on hypoxia-inducible factor (HIF) signalingand reactive oxygen species (ROS). Here, we perform genome-wide CRISPR growth screensat 21%, 5%, and 1% oxygen to systematically identify gene knockouts with relativefitness defects in high oxygen (213 genes) or low oxygen (109 genes), most withoutknown connection to HIF or ROS. Knockouts of many mitochondrial pathways thought tobe essential, including complex I and enzymes in Fe-S biosynthesis, grow relativelywell at low oxygen and thus are buffered by hypoxia. In contrast, in certain celltypes, knockout of lipid biosynthetic and peroxisomal genes causes fitness defectsonly in low oxygen. Our resource nominates genetic diseases whose severity may bemodulated by oxygen and links hundreds of genes to oxygen homeostasis.

DOI: 10.1016/j.cell.2020.03.029

编辑:小柯机器人

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