KCS1deletion inSaccharomyces cerevisiaeleads to a defect in translocation of autophagic proteins and reduces autophagosome formation
Open accessAbstract
Inositol phosphates are implicated in the regulation of autophagy; however, the exact role of each inositol phosphate species is unclear. In this study, we systematically analyzed the highly conserved inositol polyphosphate synthesis pathway in S. cerevisiae for its role in regulating autophagy. Using yeast mutants that harbored a deletion in each of the genes within the inositol polyphosphate synthesis pathway, we found that deletion of KCS1, and to a lesser degree IPK2, led to a defect in autophagy. KCS1 encodes an inositol hexakisphosphate/heptakisposphate kinase that synthesizes 5-IP(7) and IP(8); and IPK2 encodes an inositol polyphosphate multikinase required for synthesis of IP(4) and IP(5). We characterized the kcs1Δ mutant strain in detail. The kcs1Δ yeast exhibited reduced autophagic flux, which might be caused by both the reduction in autophagosome number and autophagosome size as observed under nitrogen starvation. The autophagy defect in kcs1Δ strain was associated with mislocalization of the phagophore assembly site (PAS) and a defect in Atg18 release from the vacuole membrane under nitrogen deprivation conditions. Interestingly, formation of autophagosome-like vesicles was commonly observed to originate from the plasma membrane in the kcs1Δ strain. Our results indicate that lack of KCS1 interferes with proper localization of the PAS, leads to reduction of autophagosome formation, and causes the formation of autophagosome-like structure in abnormal subcellular locations.
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IPMK plays a crucial role in autophagy.
“It plays a crucial role in cell proliferation [34], metabolism [58], autophagy [14,64], and migration [34,53,54].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [64]
The paper identifies IPK2 as an inositol polyphosphate multikinase and reports that its deletion impairs autophagy in yeast, though less than KCS1 deletion. Its findings concern autophagy induced by nitrogen deprivation in yeast, so they do not establish the unqualified claim that IPMK plays a crucial role in autophagy generally (Results and Discussion; page unavailable in our copy). (LLM, conf=0.86)
Experimental — accuracy not yet measuredIPMK depletion impairs autophagy activation in both yeast and mammalian cells.
“IPMK depletion impairs autophagy activation in both yeast [64,65] and mammalian cells [14,82].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [64]
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Kihara, A., Noda, T., Ishihara, N., & Ohsumi, Y. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.519 · Cited by 1,004 · see citing works
Plasma membrane contributes to the formation of pre-autophagosomal structures
Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C., & Rubinsztein, D. C. (2010) · Nature Cell Biology · doi:10.1038/ncb2078 · Cited by 902 · see citing works
A Role for Nuclear Inositol 1,4,5-Trisphosphate Kinase in Transcriptional Control
Odom, A. R., Stahlberg, A., Wente, S. R., & York, J. D. (2000) · Science · doi:10.1126/science.287.5460.2026 · Cited by 394 · see citing works
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“IPMK depletion impairs autophagy activation in both yeast [64,65] and mammalian cells [14,82].”
Influential
- Authors
- Taylor, Jr., Chen, P.-H., Chou, C.-C., Patel, J., & Jin, S. V.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Jin, Shengkan V.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2012-09-14
- Volume
- 8
- Issue
- 9
- Pages
- 1300-1311
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC3442877
- OpenAlex
- W2093860294
- Cited by
- 32
- References
- 3
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 2 · 2013: 3
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG030081)
- National Cancer Institute (R01CA116088)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- autophagosome formation, inositol hexakisphosphate kinase, phagophore assembly site, Atg18, nitrogen starvation, autophagic flux, protein translocation, Saccharomyces cerevisiae
- MeSH terms
- Autophagy, Cell Membrane, Inositol Phosphates, Intracellular Membranes, Microscopy, Fluorescence, Nitrogen, Phagosomes, Saccharomyces cerevisiae, Vacuoles, Gene Deletion, Phosphotransferases (Alcohol Group Acceptor), Phosphotransferases (Phosphate Group Acceptor), Protein Transport, Saccharomyces cerevisiae Proteins, Green Fluorescent Proteins
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