Mitochondrial unfolded protein response: An emerging pathway in human diseases

被引:86
作者
Zhu, Li [1 ]
Zhou, Qionglin [1 ]
He, Lu [2 ]
Chen, Linxi [1 ]
机构
[1] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China
[2] Univ South China, Affiliated Hosp 1, Dept Pharm, Hengyang, Peoples R China
基金
中国国家自然科学基金;
关键词
UPRmt; Ageing; Neurodegenerative; Cancers; Heart; Diseases; STRESS-RESPONSE; LON PROTEASE; MISFOLDED PROTEINS; HEART-DISEASE; UPR; ACTIVATION; LONGEVITY; CANCER; ATF5; PROTEOSTASIS;
D O I
10.1016/j.freeradbiomed.2020.12.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondrial unfolded protein response (UPRmt) is a mitochondria stress response, which the transcriptional activation programs of mitochondrial chaperone proteins and proteases are initiated to maintain proteostasis in mitochondria. Additionally, the activation of UPRmt delays aging and extends lifespan by maintaining mitochondrial proteostasis. Growing evidences suggests that UPRmt plays an important role in diverse human diseases, especially ageing-related diseases. Therefore, this review focuses on the role of UPRmt in ageing and ageing-related neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. The activation of UPRmt and the high expression of UPRmt components contribute to longevity extension. The activation of UPRmt may ameliorate Alzheimer's disease, Parkinson's disease and Huntington's disease. Besides, UPRmt is also involved in the occurrence and development of cancers and heart diseases. UPRmt contributes to the growth, invasive and metastasis of cancers. UPRmt has paradoxical roles in heart diseases. UPRmt not only protects against heart damage, but may sometimes aggravates the development of heart diseases. Considering the pleiotropic actions of UPRmt system, targeting UPRmt pathway may be a potent therapeutic avenue for neurodegenerative diseases, cancers and heart diseases.
引用
收藏
页码:125 / 134
页数:10
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