线粒体自噬与结直肠癌：面向精准医疗的深入探索
Mitophagy and Colorectal Cancer: An In-Depth Exploration for Precision Medicine
DOI: 10.12677/acm.2026.1651848, PDF,   
作者: 叶尔纳尔·加马力丁, 肖 乾*：浙江大学医学院附属第二医院大肠外科，恶性肿瘤预警与干预教育部重点实验室，浙江 杭州
关键词: 线粒体自噬；结直肠癌；肿瘤微环境；治疗抵抗；精准医疗；Mitophagy； Colorectal Cancer； Tumor Microenvironment； Therapeutic Resistance； Precision Medicine
摘要: 结直肠癌(Colorectal Cancer, CRC)是全球高发且疾病负担沉重的恶性肿瘤之一，其发生、进展、转移及治疗抵抗与线粒体稳态失衡密切相关。线粒体自噬(Mitophagy)作为线粒体质量控制的核心机制，通过选择性识别并清除受损或冗余线粒体，维持氧化还原稳态、代谢适配及细胞命运转换，在CRC中呈现明显的双相性与情境依赖性。本文系统综述了PINK1/Parkin依赖的泛素化通路以及BNIP3、NIX、FUNDC1、PHB2等受体介导途径的分子基础，进一步总结其在CRC早期腺瘤形成、代谢重编程、侵袭转移、治疗抵抗及肿瘤微环境重塑中的作用。重点围绕治疗抵抗，阐述线粒体自噬通过线粒体质量控制、抗凋亡保护、非编码RNA调控、代谢适应及肿瘤休眠等机制促进肿瘤细胞在治疗压力下存活。在精准医疗背景下，未来应发展亚型特异性的线粒体自噬调节药物，整合单细胞测序与空间转录组学解析肿瘤微环境异质性，并建立动态、可转化的线粒体自噬生物标志物体系，以推动相关研究从机制探索走向临床应用。
Abstract: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and imposes a sub-stantial global disease burden. Its initiation, progression, metastasis, and therapeutic resistance are closely associated with disruption of mitochondrial homeostasis. Mitophagy, a central mechanism of mitochondrial quality control, selectively recognizes and removes damaged or superfluous mitochondria, thereby maintaining redox balance, metabolic adaptation, and cell fate transitions. In CRC, mitophagy exhibits pronounced dual roles and strong context dependency. This review systematically summarizes the molecular basis of the PINK1/Parkin-dependent ubiquitin pathway as well as receptor-mediated pathways involving BNIP3, NIX, FUNDC1, and PHB2. It further discusses the roles of mitophagy in early adenoma formation, metabolic reprogramming, invasion and metastasis, therapeutic resistance, and remodeling of the tumor microenvironment in CRC. With particular emphasis on treatment resistance, we highlight that mitophagy promotes tumor cell survival under therapeutic stress through multiple mechanisms, including mitochondrial quality control, anti-apoptotic protection, non-coding RNA-mediated regulation, metabolic adaptation, and tumor dormancy. In the era of precision medicine, future efforts should focus on developing subtype-specific mitophagy-targeting agents, integrating single-cell sequencing and spatial transcriptomics to decipher tumor microenvironment heterogeneity, and establishing dynamic and clinically translatable mitophagy-related biomarker systems, thereby facilitating the translation of mechanistic insights into clinical applications.
文章引用：叶尔纳尔·加马力丁, 肖乾. 线粒体自噬与结直肠癌：面向精准医疗的深入探索[J]. 临床医学进展, 2026, 16(5): 561-567. https://doi.org/10.12677/acm.2026.1651848

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