Complex Inhibitory Effects of Nitric Oxide on Autophagy
| العنوان: | Complex Inhibitory Effects of Nitric Oxide on Autophagy |
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| المؤلفون: | Sara Imarisio, Sovan Sarkar, Andrea Williams, Guido Kroemer, Maurizio Renna, Angeleen Fleming, Cahir J. O'Kane, David C. Rubinsztein, Claudia Rose, Viktor I. Korolchuk, Shouqing Luo, Moisés García-Arencibia, Benjamin R. Underwood |
| المساهمون: | Fleming, Angeleen [0000-0003-3721-7126], Underwood, Benjamin [0000-0003-3427-9487], O'Kane, Cahir [0000-0002-3488-2078], Rubinsztein, David [0000-0001-5002-5263], Apollo - University of Cambridge Repository, Sarkar, Sovan, Korolchuk, Viktor I., Renna, Maurizio, Imarisio, Sara, Fleming, Angeleen, Mazza, WILLIAM ANDREA, Garcia-Arencibia, Moise, Rose, Claudia, Luo, Shouqing, Underwood, Benjamin R., Kroemer, Guido, O'Kane, Cahir J., Rubinsztein, David C. |
| المصدر: | Molecular Cell |
| بيانات النشر: | Cell Press, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Autophagosome, mTORC1, HeLa Cell, chemistry.chemical_compound, Mice, 0302 clinical medicine, HEK293 Cell, Enzyme Inhibitor, Protein Isoforms, Enzyme Inhibitors, Phosphorylation, Membrane Protein, Class III Phosphatidylinositol 3-Kinase, Nuclear Protein, 0303 health sciences, Huntingtin Protein, Apoptosis Regulatory Protein, biology, TOR Serine-Threonine Kinase, TOR Serine-Threonine Kinases, Neurodegeneration, Nuclear Proteins, 3. Good health, Cell biology, I-kappa B Kinase, Nitric oxide synthase, Huntington Disease, NG-Nitroarginine Methyl Ester, Proto-Oncogene Proteins c-bcl-2, Beclin-1, Human, Nerve Tissue Proteins, Mechanistic Target of Rapamycin Complex 1, Nitric Oxide, Article, Nitric oxide, Cell Line, 03 medical and health sciences, Tuberous Sclerosis Complex 2 Protein, medicine, Autophagy, Animals, Humans, Mitogen-Activated Protein Kinase 8, Molecular Biology, 030304 developmental biology, Tumor Suppressor Protein, Animal, Protein, Tumor Suppressor Proteins, AMPK, Protein Isoform, Membrane Proteins, Proteins, Cell Biology, medicine.disease, Class III Phosphatidylinositol 3-Kinases, Rats, HEK293 Cells, chemistry, Multiprotein Complexes, Nerve Tissue Protein, biology.protein, Multiprotein Complexe, Rat, Nitric Oxide Synthase, Apoptosis Regulatory Proteins, 030217 neurology & neurosurgery, HeLa Cells |
| الوصف: | Summary Autophagy, a major degradation process for long-lived and aggregate-prone proteins, affects various human processes, such as development, immunity, cancer, and neurodegeneration. Several autophagy regulators have been identified in recent years. Here we show that nitric oxide (NO), a potent cellular messenger, inhibits autophagosome synthesis via a number of mechanisms. NO impairs autophagy by inhibiting the activity of S-nitrosylation substrates, JNK1 and IKKβ. Inhibition of JNK1 by NO reduces Bcl-2 phosphorylation and increases the Bcl-2–Beclin 1 interaction, thereby disrupting hVps34/Beclin 1 complex formation. Additionally, NO inhibits IKKβ and reduces AMPK phosphorylation, leading to mTORC1 activation via TSC2. Overexpression of nNOS, iNOS, or eNOS impairs autophagosome formation primarily via the JNK1–Bcl-2 pathway. Conversely, NOS inhibition enhances the clearance of autophagic substrates and reduces neurodegeneration in models of Huntington's disease. Our data suggest that nitrosative stress-mediated protein aggregation in neurodegenerative diseases may be, in part, due to autophagy inhibition. Graphical Abstract Highlights ► NO inhibits autophagy by independently inhibiting JNK1 and IKKβ ► NO inhibits autophagic flux via mTOR and mTOR-independent routes ► NOS overexpression impairs autophagosome synthesis via JNK1–Bcl-2 pathway ► NOS inhibition induces autophagy and protects against neurodegeneration |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1097-4164 1097-2765 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::209d48dfccc0685060c450c44197eabbTest http://europepmc.org/articles/PMC3149661Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....209d48dfccc0685060c450c44197eabb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974164 10972765 |
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