Article ; Online: FKBP5/FKBP51 on weight watch: central FKBP5 links regulatory WIPI protein networks to autophagy and metabolic control.
2022 Volume 18, Issue 11, Page(s) 2756–2758
Abstract: Stress and changes in energy stores are perceived by hormone- and nutrient-sensing nuclei of the hypothalamus, which orchestrate an adaptive physiological body response to maintain homeostasis. Macroautophagy/autophagy is a fundamental lysosomal ... ...
Abstract | Stress and changes in energy stores are perceived by hormone- and nutrient-sensing nuclei of the hypothalamus, which orchestrate an adaptive physiological body response to maintain homeostasis. Macroautophagy/autophagy is a fundamental lysosomal degradation system contributing to preservation of proteome balance and metabolic homeostasis. Its dysregulation is linked to diverse human pathologies, including neuropsychiatric and metabolic disorders. Autophagy is coordinated by cellular nutrient sensors, including AMPK and MTORC1 that interact with WIPI proteins. Studies suggest that WDR45/WIPI4 interacts with the stress-sensitive co-chaperone FKBP5/FKBP51, which has emerged as a key autophagy scaffold. However, the impact of FKBP5 on autophagy signaling in response to metabolic challenges, such as a high-fat diet, is elusive. Therefore, we manipulated FKBP5 in the mediobasal hypothalamus (MBH) and studied autophagy signaling and protein interactions in their physiological context. We identified FKBP5 as a scaffold of the STK11/LKB1-AMPK complex with WDR45/WIPI4 and TSC2 with WDR45B/WIPI3 in response to metabolic challenges, positioning FKBP5 in major nutrient-sensing and autophagy-regulating networks. Intriguingly, we could demonstrate that |
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MeSH term(s) | AMP-Activated Protein Kinases/metabolism ; Autophagy/physiology ; Carrier Proteins ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Obesity/genetics ; Animals ; Mice ; Tacrolimus Binding Proteins/genetics |
Chemical Substances | AMP-Activated Protein Kinases (EC 2.7.11.31) ; Carrier Proteins ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; tacrolimus binding protein 5 (EC 5.2.1.8) ; Tacrolimus Binding Proteins (EC 5.2.1.-) |
Language | English |
Publishing date | 2022-04-19 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2454135-7 |
ISSN | 1554-8635 ; 1554-8627 |
ISSN (online) | 1554-8635 |
ISSN | 1554-8627 |
DOI | 10.1080/15548627.2022.2063006 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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