HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion.

ABSTRACT: Intestinal ischemia/reperfusion (I/R) injury is a typical pathological course in the clinic with a high morbidity rate. Recent research has pointed out the critical role of ubiquitination during the occurrence and development of intestinal I/R by precisely mediating protein quality control and function. Here, we conducted an integrated multiomic analysis to identify critical ubiquitination-associated molecules in intestinal I/R and identified endoplasmic reticulum-located HRD1 as a candidate molecule. During intestinal I/R, excessive ER stress plays a central role by causing apoptotic pathway activation. In particular, we found that ER stress-mediated apoptosis was mitigated by HRD1 knockdown in intestinal I/R mice. Mechanistically, TMEM2 was identified as a new substrate of HRD1 in intest

SUBMITTER: Zhao X 

PROVIDER: S-EPMC10879504 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature