Lee, Dain Bae, Hyunjun Oh, Dongwoo Kim, Minseop Kim, Ju-Hee Ahn, Jinchul Kang, Seok-Hyeon You, Seo-Hee Kim, Dong-Hwee Oh, Hyun Jeong Heo, Won Do Chung, Seok 2026-02-04T08:31:09Z 2026-02-04T08:31:09Z 2026-02-02 2025-12 1226-3613 https://pubs.kist.re.kr/handle/201004/154224 Although considerable research has focused on enhancing the apoptotic function of BAX for several decades, inhibition of its functionality remains relatively underexplored, despite intensive BAX activation occurring in various neurodegenerative diseases. Here we present a protein engineering approach to modulate BAX integration into the mitochondrial outer membrane, establishing a tunable strategy for antiapoptosis. Utilizing optogenetic methods that employ cryptochrome 2 and its binding partner cryptochrome-interacting basic helix loop helix 1, we achieved precise spatial control over BAX localization, a critical determinant of its function. Our results demonstrate that the engineered BAX variant is effectively incapacitated in its apoptotic function while also modulating endogenous BAX activity to enhance cellular resistance to apoptosis. These findings not only advance our understanding of BAX regulation but also offer promising prospects for the development of therapeutic strategies against apoptosis-related diseases. English Springer Nature Optogenetic engineering of BAX to control mitochondrial permeabilization and attenuate apoptosis in cells Article 10.1038/s12276-025-01605-y 1 Experimental & Molecular Medicine, v.57, no.12, pp.2972 - 2984 Experimental & Molecular Medicine 57 12 2972 2984 Y scie scopus kci ART003296488 001647880900001 2-s2.0-105025993750 Biochemistry & Molecular Biology Medicine, Research & Experimental Biochemistry & Molecular Biology Research & Experimental Medicine Article ACTIVATION PROTEIN EXPRESSION FISSION DEATH DYNAMICS BCL-2 DRP1