Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

International Journal of Molecular Sciences

Jaime M. Ross¹  Lars Olson²  Giuseppe Coppotelli¹ 

[1] Department of Neuroscience, Karolinska Institutet, Retzius väg 8, Stockholm 171 77, Sweden; E-Mail

关键词: ageing;    mitochondria;    ubiquitin;    proteasome;    ROS;   

DOI  :  10.3390/ijms160819458

来源: mdpi

【 摘 要 】

Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.