新研究發現一種檢測和減輕還原壓力的細胞機制

新研究發現一種檢測和減輕還原壓力的細胞機制

作者：

小柯機器人

發布時間：2020/9/18 15:28:59

近日，美國加州大學伯克利分校Michael Rape及其課題組，最新研究發現一種檢測和減輕還原壓力的細胞機制。這一研究成果於2020年9月16日在線發表在《細胞》上。

研究人員使用成肌細胞分化將E3連接酶CUL2^FEM1B及其底物FNIP1鑑定為還原性應激反應的核心成分。由長時間的抗氧化劑信號或線粒體失活所引起的還原性應激可恢復FNIP1中Cys殘基的氧化，並使CUL2^FEM1B識別其靶標。隨之而來的FNIP1的蛋白酶體降解可恢復線粒體活性，從而保持氧化還原穩態和幹細胞完整性。

 

因此，還原性應激反應是圍繞泛素依賴性變阻器建立的，從而調節線粒體的活性來適應氧化還原需求，並在壓力和發育信號的協調中參與代謝控制。

 

據介紹，後生生物依靠保守的應激反應途徑來緩解不利條件並保持細胞完整性。應激反應在為組織形成和修復提供終生支持的幹細胞中尤其重要，但是人們對這些保護系統如何整合到發育程序中的了解卻很少。

 

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

Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216