Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe

Sep 22, 2026

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Cancer is among the leading causes of disease-related death worldwide, and inducing programmed cell death in tumor cells by targeting key regulatory genes has become a crucial therapeutic approach alongside surgery, radiotherapy, and chemotherapy. NIX/BNIP3L, a mitochondrial outer membrane protein, can mediate apoptosis to suppress tumor growth while also promoting tumor cell survival by removing intracellular reactive oxygen species (ROS) through mitophagy. This review summarizes NIX/BNIP3L structure, function, generation and degradation mechanisms, and roles in apoptosis and mitophagy, aiming to improve understanding and treatment precision for cancer patients.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Introduction

Molecular-targeted therapy and treatment rationale

Tumor heterogeneity and limitations of current targeted therapies

NIX/BNIP3L: discovery, classification, and paradoxical functions

NIX/BNIP3L mitochondrial localization and mitophagy initiation

Review Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe Fanghui Ge 1,2, Jingxuan Shu 3, Ziqian Liu 1,2, Hong Zhang 1,2 and Jiandong Wang 4,5, * Academic Editors: Robert Zdanowski and Agata Borkowska Received: 30 December 2025 Revised: 25 January 2026 Accepted: 4 February 2026 Published: 9 February 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 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; [202022038@cmc.edu.cn](202022038@cmc.edu.cn) (F.G.) 2 Experiment Teaching Demonstration Center of Laboratory Medicine, School of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China 3 Department of Pediatrics, School of Clinical Medicine, Chengdu Medical College, Chengdu 610500, China; [18381084711@163.com](18381084711@163.com) 4 Chengdu Medical College Office of Science and Technology, Chengdu Medical College, Chengdu 610500, China 5 Key Laboratory of Nuclear and Radiation Damage Mechanisms and New Treatment Technology at Chengdu Medical College of Sichuan Province, Chengdu 610500, China * [Correspondence: wangjiandong79@cmc.edu.cn](Correspondence: wangjiandong79@cmc.edu.cn) Simple Summary As a mitochondrial outer membrane protein, NIX/BNIP3L not only mediates apoptosis to inhibit tumor growth, but also promotes tumor cell survival by eliminating intracellular ROS via mitophagy. Through a systematic summary of the gene structure of NIX, the pathways of biogenesis and degradation, the mechanisms by which it orchestrates apoptosis and mitophagy, and the roles in glioblastoma, lung cancer, hepatocellular carcinoma, breast cancer, pancreatic cancer, colorectal cancer, and hematological malignancies, we anticipate providing a novel theoretical foundation for the personalized treatment and prognosis of cancer patients. Abstract Cancer is one of the leading causes of disease-related death worldwide, and targeting key regulatory genes to induce programmed cell death in tumor cells has emerged asa crucial therapeutic strategy, following surgery, radiotherapy, and chemotherapy. As a mitochondrial outer membrane protein, NIX/BNIP3L can both mediate apoptosis to inhibit tumor cell growth and promote tumor cell survival by clearing intracellular reactive oxygen species (ROS) through mitophagy. Therefore, we summarize a brief overview of the structure and function of NIX/BNIP3L, as well as the mechanisms of NIX/BNIP3L generation and degradation, the role of NIX/BNIP3L in mediating apoptosis and mitophagy and to advance the understanding of the roles of NIX/BNIP3L in glioblastoma, lung cancer, hepatocellular carcinoma, breast cancer, pancreatic cancer, colorectal cancer and hematologic neoplasms, aiming to enhance treatment precision and improve patient outcomes. Keywords: NIX/BNIP3L; mitophagy; oxidative stress; tumors; cell death 1. Introduction Molecular-targeted therapy, recognized as the fourth major modality in cancer treatment following surgery, radiotherapy, and chemotherapy, constitutes a crucial component of molecular medicine. Molecular targeted therapies achieve anticancer effects through various mechanisms, such as inhibition of cell proliferation, metastasis, angiogenesis, and induction of apoptosis, enabling precise eradication of cancer cells while minimizing damage to normal tissues [1] . This high selectivity significantly spares normal cells, leading to a decrease in common adverse reactions associated with traditional chemotherapy, such as myelosuppression and severe alopecia, thereby substantially improving patients’ quality of life and treatment tolerance. For instance, imatinib, a tyrosine kinase inhibitor, achievesan eight-year survival rate of 87% in c

FAQs

What are the dual roles of NIX/BNIP3L in tumors?

NIX/BNIP3L can mediate apoptosis to inhibit tumor growth, and it can also promote tumor cell survival by clearing intracellular ROS via mitophagy.

How does NIX/BNIP3L contribute to mitophagy?

As a mitochondrial outer membrane protein, NIX/BNIP3L uses its N-terminal LIR motif to bind processed LC3, facilitating initiation of mitophagy.

Why is developing new therapeutic targets important?

Tumor heterogeneity and the limited proportion of patients with actionable driver mutations mean many cancers lack effective targets for existing therapies.

Sep 22, 2026

Upload by Rowan