Redox control at the ER-mitochondria interface in kidney transplantation: MAM-centered stress signaling and translational organoid platforms

作者：Baicheng Kuang, Lin Han, Sopheaktra Tan, Sokun Tan, Sopheap Bou, Yuanyuan Zhao, Yan Li, Jiasheng Yu, Nianqiao Gong · 发表于：Redox Biology · 年份：2026 · DOI：10.1016/j.redox.2026.104236 · 研究领域：Mitochondrial Function and Pathology、Endoplasmic Reticulum Stress and Disease、Coenzyme Q10 studies and effects

Kidney transplantation is inevitably accompanied by ischemia-reperfusion injury in which oxidative stress and endoplasmic reticulum (ER) stress act as tightly interconnected drivers of mitochondrial dysfunction, inflammation, and long-term graft failure. Excessive reactive oxygen species disrupt mitochondrial homeostasis, while unresolved ER stress activates maladaptive unfolded protein response signaling, together shaping tubular cell fate. Although these processes have been extensively studied, their spatial and functional integration remains incompletely understood. Growing evidence indicates that oxidative stress and ER stress converge at mitochondria-associated membranes (MAMs), where calcium signaling, redox regulation, and stress-adaptive networks are integrated. However, the dynamic and context-dependent nature of MAM remodeling remains poorly defined and difficult to investigate using conventional experimental systems. In this review, we propose a MAM-centered framework that integrates cellular stress responses, with a particular focus on ischemia-reperfusion in kidney transplantation. We further highlight therapeutic strategies targeting MAM-associated pathways, including mitochondria-directed antioxidants, ER oxidoreductases and structural and signaling proteins of MAM. In parallel, we summarize emerging kidney organoid platforms as human-relevant translational systems for modeling MAM dynamics under controlled conditions. By integrating mechanistic insights with o...