Chaperone-mediated autophagy sustains hematopoietic stem cell function
Autor: | Victor Thiruthuvanathan, Susmita Kaushik, Edward Nieves, Yun Ruei Kao, Julie A. Reisz, Qian Wang, Britta Will, Ana Maria Cuervo, Angelo D'Alessandro, Shuxian Dong, Inmaculada Tasset, Evripidis Gavathiotis, Aliona Zintiridou, Monika Dzieciatkowska, Antonio Diaz |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male 0301 basic medicine Aging autophagy Cell Chaperone-Mediated Autophagy Biology Article Linoleic Acid Mice Young Adult 03 medical and health sciences 0302 clinical medicine Chaperone-mediated autophagy lysosomes Downregulation and upregulation stem cells lipid metabolism medicine Animals Humans Rejuvenation chaperones protein quality control Cell Self Renewal Cells Cultured health care economics and organizations Aged Multidisciplinary Autophagy Middle Aged Hematopoietic Stem Cells Research Highlight humanities Cell biology Transplantation Haematopoiesis 030104 developmental biology medicine.anatomical_structure protein degradation Female Stem cell Energy Metabolism Multiple Myeloma Glycolysis 030217 neurology & neurosurgery Function (biology) |
Zdroj: | Nature Cell Res |
ISSN: | 1476-4687 0028-0836 |
Popis: | The activation of mostly quiescent haematopoietic stem cells (HSCs) is a prerequisite for life-long production of blood cells1. This process requires major molecular adaptations to allow HSCs to meet the regulatory and metabolic requirements for cell division2-4. The mechanisms that govern cellular reprograming upon stem-cell activation, and the subsequent return of stem cells to quiescence, have not been fully characterized. Here we show that chaperone-mediated autophagy (CMA)5, a selective form of lysosomal protein degradation, is involved in sustaining HSC function in adult mice. CMA is required for protein quality control in stem cells and for the upregulation of fatty acid metabolism upon HSC activation. We find that CMA activity in HSCs decreases with age and show that genetic or pharmacological activation of CMA can restore the functionality of old mouse and human HSCs. Together, our findings provide mechanistic insights into a role for CMA in sustaining quality control, appropriate energetics and overall long-term HSC function. Our work suggests that CMA may be a promising therapeutic target for enhancing HSC function in conditions such as ageing or stem-cell transplantation. |
Databáze: | OpenAIRE |
Externí odkaz: |