ESCRTing proteasomes to the lysosome
| العنوان: | ESCRTing proteasomes to the lysosome |
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| المؤلفون: | Nava Segev |
| المصدر: | PLoS Genetics, Vol 16, Iss 3, p e1008631 (2020) PLoS Genetics |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Physiology, AMP-Activated Protein Kinases, QH426-470, Biochemistry, 0302 clinical medicine, Fluorescence Microscopy, AMP-activated protein kinase, Medicine and Health Sciences, Homeostasis, Proteasome endopeptidase complex, Genetics (clinical), 0303 health sciences, Microscopy, biology, Cell Death, Organic Compounds, Monosaccharides, Eukaryota, Light Microscopy, Cell biology, Chemistry, Immunoblot Analysis, medicine.anatomical_structure, Cell Processes, Physical Sciences, Cellular Structures and Organelles, Research Article, Proteasome Endopeptidase Complex, Autophagic Cell Death, Carbohydrates, Molecular Probe Techniques, Research and Analysis Methods, 03 medical and health sciences, Lysosome, medicine, Genetics, Microautophagy, Molecular Biology Techniques, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Endosomal Sorting Complexes Required for Transport, Endoplasmic reticulum, Organic Chemistry, Chemical Compounds, Organisms, Fungi, Biology and Life Sciences, Proteins, Protein Complexes, Proteasomes, Cell Biology, Yeast, Glucose, Proteasome, Cytoplasm, Vacuoles, biology.protein, Lysosomes, Physiological Processes, 030217 neurology & neurosurgery |
| الوصف: | The ubiquitin-proteasome system regulates numerous cellular processes and is central to protein homeostasis. In proliferating yeast and many mammalian cells, proteasomes are highly enriched in the nucleus. In carbon-starved yeast, proteasomes migrate to the cytoplasm and collect in proteasome storage granules (PSGs). PSGs dissolve and proteasomes return to the nucleus within minutes of glucose refeeding. The mechanisms by which cells regulate proteasome homeostasis under these conditions remain largely unknown. Here we show that AMP-activated protein kinase (AMPK) together with endosomal sorting complexes required for transport (ESCRTs) drive a glucose starvation-dependent microautophagy pathway that preferentially sorts aberrant proteasomes into the vacuole, thereby biasing accumulation of functional proteasomes in PSGs. The proteasome core particle (CP) and regulatory particle (RP) are regulated differently. Without AMPK, the insoluble protein deposit (IPOD) serves as an alternative site that specifically sequesters CP aggregates. Our findings reveal a novel AMPK-controlled ESCRT-mediated microautophagy mechanism in the regulation of proteasome trafficking and homeostasis under carbon starvation. Author summary Protein homeostasis is critical for maintaining organismal health. The cellular dysfunction caused by accumulation and aggregation of aberrant proteins or other normally short-lived proteins is associated with aging and many human diseases, including neurodegenerative disorders, diabetes, and various types of cancer. The eukaryotic ubiquitin-proteasome system regulates numerous cellular processes and through selective protein degradation helps maintain cellular protein homeostasis under normal growth conditions. However, hundreds of cellular granules or condensates are formed during carbon starvation in yeast cells, including proteasome storage granules (PSGs). PSGs result from a massive relocation of proteasomes from the nucleus to the cytoplasm under these conditions. However, how cells regulate proteasome homeostasis under these conditions remains largely unknown. Here, we demonstrate that AMPK (AMP-activated protein kinase), a master cellular energy regulator, drives ESCRT (endosomal sorting complexes required for transport)-dependent microautophagy of aberrant proteasomes. This allows rapid re-mobilization of functional proteasomes from PSGs upon glucose refeeding. Previous studies had identified classical macroautophagy as a means of degrading proteasomes during starvation. Our work shows that direct uptake of proteasomes into the vacuole (lysosome) by microautophagy is a major means of proteasome elimination under limiting glucose conditions. |
| اللغة: | English |
| تدمد: | 1553-7404 1553-7390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f7b24da07c39bca56371981d7aa4875Test https://doaj.org/article/2a488a1e85c24a68be52664af1becbc9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3f7b24da07c39bca56371981d7aa4875 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537404 15537390 |
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