文献类型：期刊文献

英文题名：The Disrupted Mitochondrial Quality Control Network: A Unifying Mechanism and Therapeutic Target for Chemotherapy-Induced Multi-Organ Toxicity

作者：Li, Yaling[1,2];Ding, Ningning[3];Liu, Xiufan[3];Si, Qi[1];Wang, Yong[4];Li, Changtian[4];Liu, Yongqi[1,2]

第一作者：李亚玲

通信作者：Liu, YQ[1];Liu, YQ[2];Li, CT[3]

机构：[1]Gansu Univ, Gansu Univ Chinese Med, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Minist Educ Peoples Republ China, Key Lab Dun Huang Med & Transformat, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Basic Med Sch, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ, Gansu Univ Chinese Med, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Minist Educ Peoples Republ China, Key Lab Dun Huang Med & Transformat, Lanzhou 730000, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Basic Med Sch, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：15

期号：3

外文期刊名：BIOLOGY-BASEL

收录：;Scopus(收录号：2-s2.0-105029985600);WOS:【SCI-EXPANDED(收录号:WOS:001687885200001)】；

基金：This study was supported by the Gansu Province Youth Talent Project (NO. 2025NQTD11), the National Natural Science Foundation of China (No. 8226150235, NO. 82405224), Gansu Province Science and Technology Projects (No. 22JR11RA122), Gansu Provincial Program for Young PhDs' Integration into Enterprises and Industrial Parks (No. 2026QB-062), and Gansu Postdoctoral Fund (Yaling Li).

语种：英文

外文关键词：mitochondrial quality control system; chemotherapy toxicity; active compounds; organ protection; multi-target therapy

摘要：Chemotherapy remains a cornerstone of systemic cancer treatment, yet dose-limiting toxicities-cardiotoxicity, neurotoxicity, and nephrotoxicity-affect 40-80% of patients, interrupt 20-30% of treatment cycles, and double long-term mortality. We propose that these seemingly distinct organ toxicities converge on a single mechanism: selective disruption of the MQC network. MQC comprises five interdependent modules-biogenesis, dynamics, mitophagy, proteostasis, and the recently characterized migrasome-mediated mitocytosis-collectively maintaining ATP supply, redox balance, and Ca2+ homeostasis in high-demand tissues. Chemotherapeutics such as anthracyclines, platinum agents, and taxanes simultaneously repress PGC-1 alpha-driven biogenesis, hyperactivate Drp1-mediated fission, impair autophagosome-lysosome fusion, and inhibit mitocytosis, triggering mitochondrial collapse, ROS overflow, and cell death. This first-in-field review delineates organ-specific MQC pathways and catalogs druggable interventions-including small molecules, natural products, and nano-delivery systems-that restore MQC checkpoints. We present an integrated "MQC disruption-multi-organ toxicity-targeted intervention" framework, identifying Drp1 hyperactivation, late-stage mitophagy arrest, and mitocytosis inhibition as core therapeutic nodes. Targeting these pathways offers a promising strategy to decouple anticancer efficacy from off-target toxicity, potentially enabling optimized dosing, reducing treatment discontinuation, and improving long-term prognosis. Most MQC-targeted agents, however, remain in preclinical or early-phase trials.