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神经退行性疾病和癌症中的线粒体质量控制:一个共同因素,不同的治疗挑战

Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.

作者信息

Dominiak Agnieszka, Gawinek Elżbieta, Banaszek Agnieszka Anna, Wilkaniec Anna

机构信息

Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 02-097 Warsaw, Poland.

Mossakowski Medical Research Institute, Department of Cellular Signalling, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland.

出版信息

Int J Mol Sci. 2025 Sep 6;26(17):8693. doi: 10.3390/ijms26178693.

Abstract

Mitochondrial quality control (MQC) mechanisms, including proteostasis, mitophagy, mitochondrial dynamics, and biogenesis, are essential for maintaining mitochondrial function and overall cellular health. Dysregulation of these systems is a common feature of both neurodegenerative diseases and cancer, but the outcomes differ. Neurons depend strongly on healthy mitochondria and are easily damaged when MQC fails, resulting in organellar dysfunction and oxidative stress. By contrast, cancer cells often adapt by using MQC pathways to sustain survival and resist cell death. The mitochondrial unfolded protein response (mtUPR) and mitophagy are central to these processes, yet their roles are context-dependent. In neurodegeneration, activation of these pathways may help neurons survive, yet persistent stimulation can shift towards harmful effects. In cancer, these same pathways enhance metabolic flexibility, promote resistance to treatment, and support tumor progression. Although therapeutic strategies targeting MQC are being explored, their translation to the clinic is difficult, partly due to opposite effects in different diseases. The observed inverse epidemiological link between cancer and neurodegeneration may also reflect the distinct regulation of MQC pathways. A clearer understanding of these mechanisms is needed to identify new treatment strategies for disorders that are clinically distinct but share common mitochondrial defects.

摘要

线粒体质量控制(MQC)机制,包括蛋白质稳态、线粒体自噬、线粒体动力学和生物发生,对于维持线粒体功能和整体细胞健康至关重要。这些系统的失调是神经退行性疾病和癌症的共同特征,但结果有所不同。神经元强烈依赖健康的线粒体,当MQC失败时很容易受损,导致细胞器功能障碍和氧化应激。相比之下,癌细胞通常通过利用MQC途径来适应,以维持生存并抵抗细胞死亡。线粒体未折叠蛋白反应(mtUPR)和线粒体自噬是这些过程的核心,但其作用取决于具体情况。在神经退行性疾病中,这些途径的激活可能有助于神经元存活,但持续刺激可能会转向有害影响。在癌症中,这些相同的途径增强代谢灵活性,促进对治疗的抗性,并支持肿瘤进展。尽管正在探索针对MQC的治疗策略,但将其转化为临床应用却很困难,部分原因是在不同疾病中会产生相反的效果。观察到的癌症与神经退行性疾病之间的反向流行病学联系也可能反映了MQC途径的不同调节。需要更清楚地了解这些机制,以确定针对临床上不同但存在共同线粒体缺陷的疾病的新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b3/12429020/91fbdfe88129/ijms-26-08693-g001.jpg

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