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PreprintCited by 2Cell death mechanisms and regulationMitochondrial Function and PathologyPhotoreceptor and optogenetics research

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Optogenetic Engineering of BAX to Control Mitochondrial Permeabilization and Attenuate Apoptosis in Cells

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Chung, Seok, Lee, Dain, Bae, Hyunjun, Oh, Dongwoo, Ahn, Jinchul, Kim, Minseop, Kang, Seok-Hyeon, Kim, Ju-Hee, Kim, Dong-Hwee, Oh, Hyunjeong, Heo, Won Do·2025·Experimental & Molecular Medicine
DOI 10.21203/rs.3.rs-6222702/v1PMC PMC12800262

Preprint — published as 10.1038/s12276-025-01605-y · Paper page

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Abstract

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 apoptosis inhibition. 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 neurodegenerative and other apoptosis related diseases.

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Metadata

Authors
Chung, S., Lee, D., Bae, H., Oh, D., Ahn, J., Kim, M., Kang, S.-H., Kim, J.-H., Kim, D.-H., Oh, H., & Heo, W. D.
Affiliations
  • Korea University (KR)
  • Korea University
  • Korea Advanced Institute of Science and Technology (KR)
Corresponding author
Chung, Seok
ORCID
Venue
Experimental & Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2025-04-22
Volume
57
Issue
12
Pages
2972-2984
ISSN
1226-3613 (ISSN-L)
DOI
10.21203/rs.3.rs-6222702/v1
PMC
PMC12800262
OpenAlex
W7117321027
Cited by
2
References
1
Citations by year
2026: 2
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Experimental & Molecular Medicine (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation
  • National Research Foundation of Korea (RS‐2024‐00440577)
  • Ministry of Science and ICT, South Korea (20012378, RS-2024-00440577)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
Keywords
Bax, optogenetics, CRY2, CIB1, mitochondrial membrane permeabilization, apoptosis, apoptosis inhibition, protein engineering, mitochondrial outer membrane, neurodegenerative diseases
MeSH terms
Humans, Mitochondria, Permeability, Protein Engineering, Apoptosis, bcl-2-Associated X Protein, Mitochondrial Membranes, Cryptochromes, Optogenetics

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