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转录因子 EB 在线粒体质量控制中的新作用。

Emerging role of transcription factor EB in mitochondrial quality control.

机构信息

Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.

Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.

出版信息

Biomed Pharmacother. 2020 Aug;128:110272. doi: 10.1016/j.biopha.2020.110272. Epub 2020 May 22.

Abstract

Mitochondria are energy producers that play a vital role in cell survival. Mitochondrial dysfunction is involved in many diseases, including metabolic syndrome, neurodegenerative disorders, cardiomyopathies, cancer, obesity, and diabetic kidney disease, and challenges still remain in terms of treatments for these diseases. Mitochondrial quality control (MQC), which is defined as the maintenance of the quantity, morphology, and function of mitochondria, plays a pivotal role in maintaining cellular metabolic homeostasis and cell survival. Recently, growing evidence suggests that the transcription factor EB (TFEB) plays a pivotal role in MQC. Here, we systemically investigate the potential role and mechanisms of TFEB in MQC, which include the activation of mitophagy, regulation of mitochondrial biogenesis, reactive oxygen species (ROS) clearance, and the balance of mitochondria fission-fusion cycle. Importantly, we further discuss the therapeutic measures and effects aimed at TFEB on mitochondrial dysfunction-related diseases. Taken together, targeting TFEB to regulate MQC may represent an appealing therapeutic strategy for mitochondrial dysfunction related-diseases.

摘要

线粒体是细胞生存中至关重要的能量产生器。线粒体功能障碍与许多疾病有关,包括代谢综合征、神经退行性疾病、心肌病、癌症、肥胖和糖尿病肾病,针对这些疾病的治疗仍然存在挑战。线粒体质量控制(MQC)定义为维持线粒体的数量、形态和功能,在维持细胞代谢平衡和细胞生存方面起着关键作用。最近,越来越多的证据表明转录因子 EB(TFEB)在 MQC 中起着关键作用。在这里,我们系统地研究了 TFEB 在 MQC 中的潜在作用和机制,包括自噬的激活、线粒体生物发生的调节、活性氧(ROS)的清除以及线粒体分裂-融合循环的平衡。重要的是,我们进一步讨论了针对 TFEB 的治疗措施及其对与线粒体功能障碍相关疾病的影响。总之,靶向 TFEB 调节 MQC 可能是一种有吸引力的治疗线粒体功能障碍相关疾病的策略。

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