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新研究发现一种检测和减轻还原压力的细胞机制
作者：小柯机器人 发布时间：2020/9/18 15:28:59

近日，美国加州大学伯克利分校Michael Rape及其课题组，最新研究发现一种检测和减轻还原压力的细胞机制。这一研究成果于2020年9月16日在线发表在《细胞》上。

研究人员使用成肌细胞分化将E3连接酶CUL2FEM1B及其底物FNIP1鉴定为还原性应激反应的核心成分。由长时间的抗氧化剂信号或线粒体失活所引起的还原性应激可恢复FNIP1中Cys残基的氧化，并使CUL2FEM1B识别其靶标。随之而来的FNIP1的蛋白酶体降解可恢复线粒体活性，从而保持氧化还原稳态和干细胞完整性。
 
因此，还原性应激反应是围绕泛素依赖性变阻器建立的，从而调节线粒体的活性来适应氧化还原需求，并在压力和发育信号的协调中参与代谢控制。
 
据介绍，后生生物依靠保守的应激反应途径来缓解不利条件并保持细胞完整性。应激反应在为组织形成和修复提供终生支持的干细胞中尤其重要，但是人们对这些保护系统如何整合到发育程序中的了解却很少。
 
附：英文原文

Title: A Cellular Mechanism to Detect and Alleviate Reductive Stress

Author: Andrew G. Manford, Fernando Rodríguez-Pérez, Karen Y. Shih, Zhuo Shi, Charles A. Berdan, Mangyu Choe, Denis V. Titov, Daniel K. Nomura, Michael Rape

Issue&Volume: 2020-09-16

Abstract: Metazoan organisms rely on conserved stress response pathways to alleviate adverseconditions and preserve cellular integrity. Stress responses are particularly importantin stem cells that provide lifetime support for tissue formation and repair, but howthese protective systems are integrated into developmental programs is poorly understood.Here we used myoblast differentiation to identify the E3 ligase CUL2FEM1B and its substrate FNIP1 as core components of the reductive stress response. Reductivestress, as caused by prolonged antioxidant signaling or mitochondrial inactivity,reverts the oxidation of invariant Cys residues in FNIP1 and allows CUL2FEM1B to recognize its target. The ensuing proteasomal degradation of FNIP1 restores mitochondrialactivity to preserve redox homeostasis and stem cell integrity. The reductive stressresponse is therefore built around a ubiquitin-dependent rheostat that tunes mitochondrialactivity to redox needs and implicates metabolic control in coordination of stressand developmental signaling.

DOI: 10.1016/j.cell.2020.08.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31076-X

期刊信息
Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216
官方网址：https://www.cell.com/