التفاصيل البيبلوغرافية
| العنوان: |
The ubiquitin-proteasome system and autophagy: self-digestion for metabolic health. |
| المؤلفون: |
Sun-Wang, Jia Liang1,2,3 (AUTHOR) jialiang.sunwang@irbbarcelona.org, Yarritu-Gallego, Alex4,5 (AUTHOR), Ivanova, Saška1,2,3 (AUTHOR), Zorzano, Antonio1,2,3 (AUTHOR) antonio.zorzano@irbbarcelona.org |
| المصدر: |
Trends in Endocrinology & Metabolism. Aug2021, Vol. 32 Issue 8, p594-608. 15p. |
| مصطلحات موضوعية: |
*AUTOPHAGY, *TYPE 2 diabetes, *DRUG target, *UBIQUITIN ligases, *HOMEOSTASIS |
| مستخلص: |
Type 2 diabetes mellitus (T2DM) is a global health challenge. Therefore, understanding the molecular mechanisms underlying the pathophysiology of T2DM is key to improving current therapies. Loss of protein homeostasis leads to the accumulation of damaged proteins in cells, which results in tissue dysfunction. The elimination of damaged proteins occurs through the ubiquitin-proteasome system (UPS) and autophagy. In this review, we describe the mutual regulation between the UPS and autophagy and the involvement of these two proteolytic systems in metabolic dysregulation, insulin resistance, and T2DM. We propose that alterations in the UPS or autophagy contribute to triggering insulin resistance and the development of T2DM. In addition, these two pathways emerge as promising therapeutic targets for improving insulin resistance. Alterations in the ubiquitin-proteasome system (UPS) and autophagy are associated with metabolic disorders, including obesity and type 2 diabetes. The proteasome activity is downregulated in liver, pancreas, and adipose tissue under insulin resistant conditions and the proteasome is required for the metabolic activity of brown adipocytes and for β-cell function. A deficient autophagy triggers insulin resistance in liver and it leads to varying alterations in conferring susceptibility to obesity and on adipogenesis. The UPS and autophagy regulate each other. The 26S proteasome is regulated by autophagy activity through a process named proteaphagy. Autophagy activity is controlled through the action of E3 ubiquitin ligases and deubiquitinases that participate in the different phases of autophagosome formation and fusion with lysosomes. Therapeutic interventions targeting the UPS and autophagy improve metabolic health. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
