Intracellular membranes are crucial for various physiological functions. This research investigates the cellular responses to intracellular membrane-focused oxidative stress using an amphiphilic photocatalyst (BTP). BTP localizes within intracellular membranes, generating hydroxyl radicals and hydrogen peroxides, leading to oxidative damage of membrane proteins, particularly those involved in protein quality control. This damage causes mitochondrial and endoplasmic reticulum stress, activating non-canonical inflammasome caspases (4 and 5), GSDMD cleavage, and ultimately, pyroptosis. The study demonstrates that oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.

Chaiheon Lee, Mingyu Park, W. C. Bhashini Wijesinghe, Seungjin Na, Chae Gyu Lee, Eunhye Hwang, Gwangsu Yoon, Jeong Kyeong Lee, Deok-Ho Roh, Yoon Hee Kwon, Jihyeon Yang, Sebastian A. Hughes, James E. Vince, Jeong Kon Seo, Duyoung Min, Tae-Hyuk Kwon