Mitochondrial unfolded protein response: An emerging pathway in human diseases

Mitochondrial unfolded protein response (UPR^mt) 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 UPR^mt delays aging and extends lifespan by maintaining mitochondrial proteostasis. Growing evidences suggests that UPR^mt plays an important role in diverse human diseases, especially ageing-related diseases. Therefore, this review focuses on the role of UPR^mt in ageing and ageing-related neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. The activation of UPR^mt and the high expression of UPR^mt components contribute to longevity extension. The activation of UPR^mt may ameliorate Alzheimer's disease, Parkinson's disease and Huntington's disease. Besides, UPR^mt is also involved in the occurrence and development of cancers and heart diseases. UPR^mt contributes to the growth, invasive and metastasis of cancers. UPR^mt has paradoxical roles in heart diseases. UPR^mt not only protects against heart damage, but may sometimes aggravates the development of heart diseases. Considering the pleiotropic actions of UPR^mt system, targeting UPR^mt pathway may be a potent therapeutic avenue for neurodegenerative diseases, cancers and heart diseases.