Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes
Open accessAbstract
In rat hepatocytes, autophagy is known to be inhibited by amino acids. Insulin and cell swelling promote inhibition by amino acids. Each of the conditions leading to inhibition of autophagic proteolysis was found to be associated with phosphorylation of a 31-kDa protein that we identified as ribosomal protein S6. A combination of leucine, tyrosine, and phenylalanine, which efficiently inhibits autophagic proteolysis, was particularly effective in stimulating S6 phosphorylation. The relationship between the percentage inhibition of proteolysis and the degree of S6 phosphorylation was linear. Thus, inhibition of autophagy and phosphorylation of S6 are under the control of the same signal transduction pathway. Stimulation of S6 phosphorylation by the presence of amino acids was due to activation of S6 kinase and not to inhibition of S6 phosphatase. The inhibition by amino acids of both autophagic proteolysis and autophagic sequestration of electro-injected cytosolic [14C]sucrose was partially prevented by rapamycin, a compound known to inhibit activation of p70 S6 kinase. In addition, rapamycin partially inhibited the rate of protein synthesis. We conclude that the fluxes through the autophagic and protein synthetic pathways are regulated in an opposite manner by the degree to which S6 is phosphorylated. Possible mechanisms by which S6 phosphorylation can cause inhibition of autophagy are discussed.
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Loss of pS6 promotes autophagosome formation.
“Loss of pS6 promotes autophagosome formation [69].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [69]
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- Authors
- Blommaart, E. F. C., Luiken, J. J. F. P., Blommaart, P. J. E., van Woerkom, G. M., & Meijer, A. J.
- Affiliations
- University of Amsterdam (NL)
- Corresponding author
- Meijer, Alfred J.
- ORCID
- Luiken, Joost J.F.P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-02
- Volume
- 270
- Issue
- 5
- Pages
- 2320-2326
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2013381376
- Cited by
- 686
- References
- 39
- Citations by year
- 2026: 15 · 2025: 11 · 2024: 17 · 2023: 15 · 2022: 14 · 2021: 28 · 2020: 23 · 2019: 18 · 2018: 26 · 2017: 33 · 2016: 30 · 2015: 30 · 2014: 29 · 2013: 34 · 2012: 40
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- ribosomal protein S6, S6 phosphorylation, autophagy inhibition, hepatocytes, amino acid inhibition, S6 kinase, p70 S6 kinase, rapamycin, signal transduction, protein synthesis, cell swelling, insulin
- MeSH terms
- Adenine, Animals, Autophagy, Male, Phosphorylation, Polyenes, Proteins, Ribosomal Proteins, Ribosomes, Rats, Wistar, Sirolimus, Ribosomal Protein S6, Rats
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