Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H2O2-Induced Oxidative Stress.

Overview

Authors: Fanghui Ge^1,2, Jingxuan Shu³, Ziqian Liu^1,2, Haixiang Ma^1,2, Minghong Cai⁴, Xinyan Deng^1,2, Hong Zhang^1,2, Jiandong Wang^5,6

ORCID iDs: Ziqian Liu, Jiandong Wang

Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-Origin Food, School of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China; (F.G.); (Z.L.); (H.M.); (X.D.); (H.Z.)
Experiment Teaching Demonstration Center of Laboratory Medicine, School of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China
Department of Pediatrics, School of Clinical Medicine, Chengdu Medical College, Chengdu 610500, China
School of Bioscience and Technology, Chengdu Medical College, Chengdu 610500, China
Chengdu Medical College Office of Science and Technology, Chengdu 610500, China
Key Laboratory of Nuclear and Radiation Damage Mechanisms and New Treatment Technology at Chengdu Medical College, Chengdu 610500, China

Institutions: Chengdu Medical College (China)

Journal: Biology, volume 15, issue 11, article 867

Dates: received 18 April 2026; accepted 29 May 2026; published online 31 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.3390/biology15110867 · PMID 42274518 · PMCID PMC13255857 · OpenAlex W7163389485

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: rat (organism), cellular / molecular (subfield)

Methods: Statistics, Connectivity

Keywords: NIX/BNIP3L, oxidative stress, mitophagy, apoptosis

Topic: Mitochondrial Function and Pathology (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: Key Project of Sichuan Higher Education Talent Training Quality and Teaching Reform (2024-2026) (JG2024-0999); the Innovation and Entrepreneurship Training Program for College Students of Chengdu Medical College (202313705023, S202513705043); the Science and Technology Foundation of Chengdu Medical College (CYZYB22-15)

Citations: cited by 1 paper (Europe PMC); 52 references in the paper

Abstract

Oxidative stress is a major contributor to neuronal apoptosis and subsequent neurofunctional deficits. This study investigates the dual role of the mitochondrial membrane-anchored protein NIX in PC12 cells, a model for mature neurons. We demonstrate that both overexpression and knockdown of NIX attenuate apoptosis under oxidative stress, albeit through distinct mechanisms. Overexpression of NIX promotes cell survival by activating NIX-mediated mitophagy, which clears damaged mitochondria and intracellular reactive oxygen species (ROS), thereby maintaining redox homeostasis. Conversely, knockdown of NIX reduces apoptosis primarily by diminishing the intrinsic pro-apoptotic function of the protein. Collectively, these findings reveal that NIX expression levels critically gate PC12 cell fate under oxidative stress by differentially activating pro-survival or anti-apoptotic pathways.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

geo:GSE104704, at NCBI GEO; found in the text, “2.13. Correlation Analysis Between ARMCX3 and…”

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 4 keywords, 3 funders, 52 references.

Cite

This paper

Ge, F., Shu, J., Liu, Z., Ma, H., Cai, M., Deng, X., Zhang, H., & Wang, J. (2026). Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H2O2-Induced Oxidative Stress. Biology, 15(11), 867. https://doi.org/10.3390/biology15110867

BibTeX

@article{ge2026differential, author = {Ge, Fanghui and Shu, Jingxuan and Liu, Ziqian and Ma, Haixiang and Cai, Minghong and Deng, Xinyan and Zhang, Hong and Wang, Jiandong}, title = {{Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H\<sub\>2\</sub\>O\<sub\>2\</sub\>-Induced Oxidative Stress}}, journal = {Biology}, year = {2026}, month = may, volume = {15}, number = {11}, pages = {867}, publisher = {Multidisciplinary Digital Publishing Institute (MDPI)}, issn = {2079-7737}, doi = {10.3390/biology15110867}, url = {https://doi.org/10.3390/biology15110867}, pmid = {42274518}, pmcid = {PMC13255857} }

RIS

TY - JOUR AU - Ge, Fanghui AU - Shu, Jingxuan AU - Liu, Ziqian AU - Ma, Haixiang AU - Cai, Minghong AU - Deng, Xinyan AU - Zhang, Hong AU - Wang, Jiandong TI - Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H2O2-Induced Oxidative Stress T2 - Biology J2 - Biology (Basel) PY - 2026 DA - 2026/05/31 VL - 15 IS - 11 SP - 867 SN - 2079-7737 PB - Multidisciplinary Digital Publishing Institute (MDPI) DO - 10.3390/biology15110867 UR - https://doi.org/10.3390/biology15110867 LA - en ER -

CSL-JSON

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Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H<sub>2</sub>O<sub>2</sub>-Induced Oxidative Stress.

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Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;-Induced Oxidative Stress.

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Differential Activation of Pro-Survival Pathways by NIX/BNIP3L: An Expression-Level-Dependent Mechanism Governing PC12 Cell Fate During H<sub>2</sub>O<sub>2</sub>-Induced Oxidative Stress.