AMPK regulates phagophore-to-autophagosome maturation.
| Autor: | Barnaba C; Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing, MI, USA., Broadbent DG; Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing, MI, USA.; College of Osteopathic Medicine, Michigan State University , East Lansing, MI, USA.; Department of Physiology, Michigan State University, East Lansing, MI, USA., Kaminsky EG; Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing, MI, USA., Perez GI; Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing, MI, USA., Schmidt JC; Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing, MI, USA.; Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI, USA. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of cell biology [J Cell Biol] 2024 Aug 05; Vol. 223 (8). Date of Electronic Publication: 2024 May 22. |
| DOI: | 10.1083/jcb.202309145 |
| Abstrakt: | Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation. Autophagy can be activated by nutrient stress, for example, by a reduction in the cellular levels of amino acids. In contrast, how autophagy is regulated by low cellular ATP levels via the AMP-activated protein kinase (AMPK), an important therapeutic target, is less clear. Using live-cell imaging and an automated image analysis pipeline, we systematically dissect how nutrient starvation regulates autophagosome biogenesis. We demonstrate that glucose starvation downregulates autophagosome maturation by AMPK-mediated inhibition of phagophore tethering to donor membrane. Our results clarify AMPKs regulatory role in autophagy and highlight its potential as a therapeutic target to reduce autophagy. (© 2024 Barnaba et al.) |
| Databáze: | MEDLINE |
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