Cited by 32Autophagy in Disease and TherapyFungal and yeast genetics researchCellular transport and secretion

KCS1deletion inSaccharomyces cerevisiaeleads to a defect in translocation of autophagic proteins and reduces autophagosome formation

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Taylor, Jr., Robert, Chen, Po-Hao, Chou, Chia-Ching, Patel, Jasmin, Jin, Shengkan V.·2012·Autophagy

Abstract

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 measured
  • IPMK 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].”

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Research works printed but not linked: 47

  1. Krick R, Tolstrup J, Appelles A, Henke S, Thumm M. The relevance of the phosphatidylinositolphosphat- binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy. FEBS Lett 2006; 580:4632-8; PMID:16876790; http://dx.doi.org/10.1016/j.febs- let.2006.07.041 · DOI
  2. Nagata E, Saiardi A, Tsukamoto H, Satoh T, Itoh Y, Itoh J, et al. Inositol hexakisphosphate kinases promote autophagy. Int J Biochem Cell Biol 2010; 42:2065- 71; PMID:20883817; http://dx.doi.org/10.1016/j. biocel.2010.09.013 · DOI
  3. Sarkar S, Rubinsztein DC. Inositol and IP3 levels regu- late autophagy: biology and therapeutic speculations. Autophagy 2006; 2:132-4; PMID:16874097
  4. Sarkar S, Floto RA, Berger Z, Imarisio S, Cordenier A, Pasco M, et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol 2005; 170:1101-11; PMID:16186256; http://dx.doi. org/10.1083/jcb.200504035 · DOI · Paper page
  5. Kanki T, Wang K, Klionsky DJ. A genomic screen for yeast mutants defective in mitophagy. Autophagy 2010; 6:278-80; PMID:20364111; http://dx.doi. org/10.4161/auto.6.2.10901 · DOI
  6. Shintani T, Klionsky DJ. Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vac- uole targeting pathway. J Biol Chem 2004; 279:29889- 94; PMID:15138258; http://dx.doi.org/10.1074/jbc. M404399200 · DOI
  7. Noda T, Matsuura A, Wada Y, Ohsumi Y. Novel system for monitoring autophagy in the yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun 1995; 210:126-32; PMID:7741731; http://dx.doi. org/10.1006/bbrc.1995.1636 · DOI
  8. Suzuki K, Kubota Y, Sekito T, Ohsumi Y. Hierarchy of Atg proteins in pre-autophagosomal structure organiza- tion. Genes Cells 2007; 12:209-18; PMID:17295840; http://dx.doi.org/10.1111/j.1365-2443.2007.01050.x · DOI
  9. Rieder SE, Emr SD. A novel RING finger protein complex essential for a late step in protein transport to the yeast vacuole. Mol Biol Cell 1997; 8:2307-27; PMID:9362071
  10. Yen W-L, Shintani T, Nair U, Cao Y, Richardson BC, Li Z, et al. The conserved oligomeric Golgi complex is involved in double-membrane vesicle for- mation during autophagy. J Cell Biol 2010; 188:101- 14; PMID:20065092; http://dx.doi.org/10.1083/ jcb.200904075 · DOI
  11. Sakane H, Yamamoto T, Tanaka K. The functional relationship between the Cdc50p-Drs2p putative ami- nophospholipid translocase and the Arf GAP Gcs1p in vesicle formation in the retrieval pathway from yeast early endosomes to the TGN. Cell Struct Funct 2006; 31:87-108; PMID:17062999; http://dx.doi. org/10.1247/csf.06021 · DOI
  12. Meiling-Wesse K, Barth H, Voss C, Eskelinen E-L, Epple UD, Thumm M. Atg21 is required for effec- tive recruitment of Atg8 to the preautophagosom- al structure during the Cvt pathway. J Biol Chem 2004; 279:37741-50; PMID:15194695; http://dx.doi. org/10.1074/jbc.M401066200 · DOI
  13. Strømhaug PE, Reggiori F, Guan J, Wang C-W, Klionsky DJ. Atg21 is a phosphoinositide binding protein required for efficient lipidation and localiza- tion of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol Biol Cell 2004; 15:3553- 66; PMID:15155809; http://dx.doi.org/10.1091/mbc. E04-02-0147 · DOI
  14. Obara K, Ohsumi Y. PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast. J Lipids 2011; 2011:498768; PMID:21490802; http://dx.doi. org/10.1155/2011/498768 · DOI
  15. Cuervo AM. The plasma membrane brings auto- phagosomes to life. Nat Cell Biol 2010; 12:735- 7; PMID:20680002; http://dx.doi.org/10.1038/ ncb0810-735 · DOI
  16. Saiardi A, Caffrey JJ, Snyder SH, Shears SB. Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett 2000; 468:28-32; PMID:10683435; http:// dx.doi.org/10.1016/S0014-5793(00)01194-7 · DOI · Paper page
  17. Auesukaree C, Tochio H, Shirakawa M, Kaneko Y, Harashima S. Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis, are essen- tial for phosphate regulation and polyphosphate accu- mulation in Saccharomyces cerevisiae. J Biol Chem 2005; 280:25127-33; PMID:15866881; http://dx.doi. org/10.1074/jbc.M414579200 · DOI
  18. Wang C-W, Klionsky DJ. The molecular mechanism of autophagy. Mol Med 2003; 9:65-76; PMID:12865942.
  19. Suzuki K, Ohsumi Y. Molecular machinery of auto- phagosome formation in yeast, Saccharomyces cerevi- siae. FEBS Lett 2007; 581:2156-61; PMID:17382324; http://dx.doi.org/10.1016/j.febslet.2007.01.096 · DOI
  20. Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 2010; 22:124-31; PMID:20034776; http://dx.doi.org/10.1016/j.ceb.2009.11.014 · DOI · Paper page
  21. Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 1998; 273:3963-6; PMID:9461583; http://dx.doi. org/10.1074/jbc.273.7.3963 · DOI
  22. Yang Z, Geng J, Yen W-L, Wang K, Klionsky DJ. Positive or negative roles of different cyclin-dependent kinase Pho85-cyclin complexes orchestrate induction of autophagy in Saccharomyces cerevisiae. Mol Cell 2010; 38:250-64; PMID:20417603; http://dx.doi. org/10.1016/j.molcel.2010.02.033 · DOI
  23. Wang Z, Wilson WA, Fujino MA, Roach PJ. Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP- activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol Cell Biol 2001; 21:5742-52; PMID:11486014; http://dx.doi.org/10.1128/ MCB.21.17.5742-5752.2001 · DOI
  24. Budovskaya YV, Stephan JS, Reggiori F, Klionsky DJ, Herman PK. The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the auto- phagy process in Saccharomyces cerevisiae. J Biol Chem 2004; 279:20663-71; PMID:15016820; http://dx.doi. org/10.1074/jbc.M400272200 · DOI
  25. Yorimitsu T, Zaman S, Broach JR, Klionsky DJ. Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae. Mol Biol Cell 2007; 18:4180-9; PMID:17699586; http://dx.doi. org/10.1091/mbc.E07-05-0485 · DOI
  26. Tallóczy Z, Jiang W, Virgin HW 4 th , Leib DA, Scheuner D, Kaufman RJ, et al. Regulation of starva- tion-and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci U S A 2002; 99:190-5; PMID:11756670; http://dx.doi. org/10.1073/pnas.012485299 · DOI
  27. Obara K, Noda T, Niimi K, Ohsumi Y. Transport of phosphatidylinositol 3-phosphate into the vacuole via autophagic membranes in Saccharomyces cerevi- siae. Genes Cells 2008; 13:537-47; PMID:18533003; http://dx.doi.org/10.1111/j.1365-2443.2008.01188.x · DOI
  28. Obara K, Sekito T, Niimi K, Ohsumi Y. The Atg18- Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J Biol Chem 2008; 283:23972- 80; PMID:18586673; http://dx.doi.org/10.1074/jbc. M803180200 · DOI
  29. Nair U, Cao Y, Xie Z, Klionsky DJ. Roles of the lipid- binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole targeting pathway and autophagy. J Biol Chem 2010; 285:11476-88; PMID:20154084; http://dx.doi. org/10.1074/jbc.M109.080374 References · DOI
  30. Lee Y-S, Mulugu S, York JD, O'Shea EK. Regulation of a cyclin-CDK-CDK inhibitor complex by ino- sitol pyrophosphates. Science 2007; 316:109-12; PMID:17412959; http://dx.doi.org/10.1126/sci- ence.1139080 · DOI
  31. Luo HR, Huang YE, Chen JC, Saiardi A, Iijima M, Ye K, et al. Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain- PtdIns(3,4,5)P3 interactions. Cell 2003; 114:559-72; PMID:13678580; http://dx.doi.org/10.1016/S0092- 8674(03)00640-8 · DOI
  32. Falasca M, Chiozzotto D, Godage HY, Mazzoletti M, Riley AM, Previdi S, et al. A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate. Br J Cancer 2010; 102:104-14; PMID:20051961; http://dx.doi. org/10.1038/sj.bjc.6605408 · DOI
  33. Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, et al. Inositol pyrophos- phates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 2010; 143:897- 910; PMID:21145457; http://dx.doi.org/10.1016/j. cell.2010.11.032 · DOI
  34. Dubois E, Scherens B, Vierendeels F, Ho MMW, Messenguy F, Shears SB. In Saccharomyces cerevi- siae, the inositol polyphosphate kinase activity of Kcs1p is required for resistance to salt stress, cell wall integrity, and vacuolar morphogenesis. J Biol Chem 2002; 277:23755-63; PMID:11956213; http://dx.doi. org/10.1074/jbc.M202206200 · DOI
  35. Saiardi A, Sciambi C, McCaffery JM, Wendland B, Snyder SH. Inositol pyrophosphates regulate endocytic trafficking. Proc Natl Acad Sci U S A 2002; 99:14206- 11; PMID:12391334; http://dx.doi.org/10.1073/ pnas.212527899 · DOI
  36. Morrison BH, Bauer JA, Kalvakolanu DV, Lindner DJ. Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. J Biol Chem 2001; 276:24965- 70; PMID:11337497; http://dx.doi.org/10.1074/jbc. M101161200 · DOI
  37. Saiardi A, Resnick AC, Snowman AM, Wendland B, Snyder SH. Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases. Proc Natl Acad Sci U S A 2005; 102:1911-4; PMID:15665079; http:// dx.doi.org/10.1073/pnas.0409322102 · DOI
  38. York SJ, Armbruster BN, Greenwell P, Petes TD, York JD. Inositol diphosphate signaling regulates telomere length. J Biol Chem 2005; 280:4264-9; PMID:15561716; http://dx.doi.org/10.1074/jbc. M412070200 · DOI
  39. Bhandari R, Saiardi A, Ahmadibeni Y, Snowman AM, Resnick AC, Kristiansen TZ, et al. Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event. Proc Natl Acad Sci U S A 2007; 104:15305-10; PMID:17873058; http://dx.doi. org/10.1073/pnas.0707338104 · DOI
  40. Saiardi A, Bhandari R, Resnick AC, Snowman AM, Snyder SH. Phosphorylation of proteins by inositol pyrophosphates. Science 2004; 306:2101- 5; PMID:15604408; http://dx.doi.org/10.1126/sci- ence.1103344 · DOI
  41. York JD, Odom AR, Murphy R, Ives EB, Wente SR. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 1999; 285:96-100; PMID:10390371; http://dx.doi.org/10.1126/science.285.5424.96 · DOI
  42. Baudin A, Ozier-Kalogeropoulos O, Denouel A, Lacroute F, Cullin C. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res 1993; 21:3329-30; PMID:8341614; http://dx.doi.org/10.1093/nar/21.14.3329 · DOI
  43. Kanki T, Wang K, Baba M, Bartholomew CR, Lynch- Day MA, Du Z, et al. A genomic screen for yeast mutants defective in selective mitochondria autophagy. Mol Biol Cell 2009; 20:4730-8; PMID:19793921; http://dx.doi.org/10.1091/mbc.E09-03-0225 · DOI · Paper page
  44. Rue SM, Mattei S, Saksena S, Emr SD. Novel Ist1- Did2 complex functions at a late step in multive- sicular body sorting. Mol Biol Cell 2008; 19:475-84; PMID:18032584; http://dx.doi.org/10.1091/mbc. E07-07-0694 · DOI
  45. Gietz RD, Schiestl RH. Quick and easy yeast transfor- mation using the LiAc/SS carrier DNA/PEG method. Nat Protoc 2007; 2:35-7; PMID:17401335; http:// dx.doi.org/10.1038/nprot.2007.14 · DOI
  46. Darsow T, Rieder SE, Emr SD. A multispecificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. J Cell Biol 1997; 138:517-29; PMID:9245783; http:// dx.doi.org/10.1083/jcb.138.3.517 · DOI
  47. Kim J, Huang W-P, Klionsky DJ. Membrane recruit- ment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol 2001; 152:51-64; PMID:11149920; http://dx.doi. org/10.1083/jcb.152.1.51 · DOI

Cited by

Sorted by citations

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
Published
2012-09-14
Volume
8
Issue
9
Pages
1300-1311
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
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
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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