The propeptide of yeast cathepsin D inhibits programmed necrosis
Open accessAbstract
The lysosomal endoprotease cathepsin D (CatD) is an essential player in general protein turnover and specific peptide processing. CatD-deficiency is associated with neurodegenerative diseases, whereas elevated CatD levels correlate with tumor malignancy and cancer cell survival. Here, we show that the CatD ortholog of the budding yeast Saccharomyces cerevisiae (Pep4p) harbors a dual cytoprotective function, composed of an anti-apoptotic part, conferred by its proteolytic capacity, and an anti-necrotic part, which resides in the protein's proteolytically inactive propeptide. Thus, deletion of PEP4 resulted in both apoptotic and necrotic cell death during chronological aging. Conversely, prolonged overexpression of Pep4p extended chronological lifespan specifically through the protein's anti-necrotic function. This function, which triggered histone hypoacetylation, was dependent on polyamine biosynthesis and was exerted via enhanced intracellular levels of putrescine, spermidine and its precursor S-adenosyl-methionine. Altogether, these data discriminate two pro-survival functions of yeast CatD and provide first insight into the physiological regulation of programmed necrosis in yeast.
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S. cerevisiae was also found to undergo a form of programmed necrosis.
“Saccharomyces cerevisiae was also found to undergo a form of programmed necrosis (Carmona-Gutierrez et al., 2011).”
From Programmed cell death in aging (2015) · cites this paper as Carmona-Gutierrez et al., 2011
Over-expression of Pep4 increased chronological life span associated with decreased necrotic-like PCD.
“In turn, over-expression of Pep4 increased chronological life span associated with decreased necrotic-like PCD.”
From Programmed cell death in aging (2015) · cites this paper as Carmona-Gutierrez et al., 2011
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- Authors
- Carmona-Gutiérrez, D., Bauer, M. A., Ring, J., Knauer, H., Eisenberg, T., Büttner, S., Ruckenstuhl, C., Reisenbichler, A., Magnes, C., Rechberger, G. N., Birner-Gruenberger, R., Jungwirth, H., Fröhlich, K.-U., Sinner, F., Kroemer, G., & Madeo, F.
- Affiliations
- University of Graz (AT)
- Joanneum Research (AT)
- Inserm (FR)
- Corresponding author
- Madeo, F
- ORCID
- Venue
- Cell Death & Disease
- Published
- 2011-05-19
- Volume
- 2
- Issue
- 5
- Pages
- e161-e161
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3122122
- OpenAlex
- W1988468826
- Cited by
- 69
- References
- 41
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 7 · 2018: 2 · 2017: 7 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 12
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- European Commission
- Agence Nationale de la Recherche
- Austrian Science Fund (S9304-B05)
- Institut National Du Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- cathepsin D, propeptide, necroptosis, chronological aging, chronological lifespan, apoptosis, histone hypoacetylation, polyamine biosynthesis, putrescine, spermidine, S-adenosylmethionine, Saccharomyces cerevisiae, lysosomal proteases
- MeSH terms
- Acetylation, Cathepsin D, Cell Survival, Histones, Lysosomes, Necrosis, Plasmids, Protein Precursors, Saccharomyces cerevisiae, Transfection, Protein Engineering, Biogenic Polyamines, Gene Expression, Aspartic Acid Endopeptidases, Cellular Senescence, Apoptosis, Gene Deletion, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins
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