Gene Symbol: ISC1
Description: inositol phosphosphingolipid phospholipase
Alias: inositol phosphosphingolipid phospholipase
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Teixeira V, Medeiros T, Vilaça R, Ferreira J, Moradas Ferreira P, Costa V. Ceramide signaling targets the PP2A-like protein phosphatase Sit4p to impair vacuolar function, vesicular trafficking and autophagy in Isc1p deficient cells. Biochim Biophys Acta. 2016;1861:21-33 pubmed publisher
    ..The isc1Δ cells also exhibit defective Cvt and vesicular trafficking in a Sit4p-dependent manner, ultimately ..
  2. De Block J, Szopinska A, Guerriat B, Dodzian J, Villers J, Hochstenbach J, et al. Yeast Pmp3p has an important role in plasma membrane organization. J Cell Sci. 2015;128:3646-59 pubmed publisher
    ..These genetic interactions, together with lipid binding assays and epifluorescence microscopy, as well as other biochemical experiments, suggest that Pmp3p could be part of a phosphoinositide-regulated stress sensor. ..
  3. Gururaj C, Federman R, Federman R, Chang A. Orm proteins integrate multiple signals to maintain sphingolipid homeostasis. J Biol Chem. 2013;288:20453-63 pubmed publisher
    ..Conversely, the calcium- and calcineurin-dependent pathway signals ER stress response upon lipid dysregulation in the absence of the Orm proteins to restore ER homeostasis. ..
  4. Barbosa A, Graça J, Mendes V, Chaves S, Amorim M, Mendes M, et al. Activation of the Hog1p kinase in Isc1p-deficient yeast cells is associated with mitochondrial dysfunction, oxidative stress sensitivity and premature aging. Mech Ageing Dev. 2012;133:317-30 pubmed publisher
    ..The hydrogen peroxide sensitivity and premature aging of isc1? cells was partially suppressed by HOG1 deletion...
  5. Kitagaki H, Cowart L, Matmati N, Montefusco D, Gandy J, de Avalos S, et al. ISC1-dependent metabolic adaptation reveals an indispensable role for mitochondria in induction of nuclear genes during the diauxic shift in Saccharomyces cerevisiae. J Biol Chem. 2009;284:10818-30 pubmed publisher
    ..Initial studies revealed that yeast cells deleted in ISC1, the gene encoding inositol sphingolipid phospholipase C, which resides in mitochondria in the post-diauxic phase, ..
  6. Guan X, Souza C, Pichler H, Dewhurst G, Schaad O, Kajiwara K, et al. Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Mol Biol Cell. 2009;20:2083-95 pubmed publisher
  7. Sawai H, Okamoto Y, Luberto C, Mao C, Bielawska A, Domae N, et al. Identification of ISC1 (YER019w) as inositol phosphosphingolipid phospholipase C in Saccharomyces cerevisiae. J Biol Chem. 2000;275:39793-8 pubmed
    ..Here we show that ISC1 (YER019w), which has homology to bacterial neutral sphingomyelinase (SMase), encodes IPS phospholipase C (IPS-PLC)...
  8. Vaena De Avalos S, Su X, Zhang M, Okamoto Y, Dowhan W, Hannun Y. The phosphatidylglycerol/cardiolipin biosynthetic pathway is required for the activation of inositol phosphosphingolipid phospholipase C, Isc1p, during growth of Saccharomyces cerevisiae. J Biol Chem. 2005;280:7170-7 pubmed
    ..In this study the in vivo mechanisms of activation and function of Isc1p were investigated. Deletion of ISC1 resulted in markedly lower growth in non-fermentable carbon sources...
  9. Matmati N, Metelli A, Tripathi K, Yan S, Mohanty B, Hannun Y. Identification of C18:1-phytoceramide as the candidate lipid mediator for hydroxyurea resistance in yeast. J Biol Chem. 2013;288:17272-84 pubmed publisher
    Recent studies showed that deletion of ISC1, the yeast homologue of the mammalian neutral sphingomyelinase, resulted in an increased sensitivity to hydroxyurea (HU)...

More Information


  1. Matmati N, Hannun Y. Thematic review series: sphingolipids. ISC1 (inositol phosphosphingolipid-phospholipase C), the yeast homologue of neutral sphingomyelinases. J Lipid Res. 2008;49:922-8 pubmed publisher
    ..82: 27-44). nSMase in mammals is represented by its homolog, inositol phosphosphingolipase C, codified by ISC1 in Saccharomyces cerevisiae (Sc) and Cryptococcus neoformans (Cn) and by CSS1 (Can't Stop Synthesizing cell wall) ..
  2. Barbosa A, Pereira C, Osorio H, Moradas Ferreira P, Costa V. The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation. Cell Cycle. 2016;15:1620-30 pubmed publisher
    ..Consistently, the activation of Sit4p in isc1? mutants, which has been associated with premature aging, leads to Hxk2p hypophosphorylation, and the expression of ..
  3. Tripathi K, Matmati N, Zheng W, Hannun Y, Mohanty B. Cellular morphogenesis under stress is influenced by the sphingolipid pathway gene ISC1 and DNA integrity checkpoint genes in Saccharomyces cerevisiae. Genetics. 2011;189:533-47 pubmed publisher
    ..We find that the sphingolipid pathway gene ISC1, the product of which catalyzes the generation of bioactive ceramides from complex sphingolipids, plays a novel ..
  4. Barbosa A, Osorio H, Sims K, Almeida T, Alves M, Bielawski J, et al. Role for Sit4p-dependent mitochondrial dysfunction in mediating the shortened chronological lifespan and oxidative stress sensitivity of Isc1p-deficient cells. Mol Microbiol. 2011;81:515-27 pubmed publisher
    ..protein phosphatase in yeast, abolished the premature ageing and hydrogen peroxide sensitivity of isc1? cells. SIT4 deletion also abolished the respiratory defects and catalase A deficiency exhibited by isc1? mutants...
  5. Matmati N, Kitagaki H, Montefusco D, Mohanty B, Hannun Y. Hydroxyurea sensitivity reveals a role for ISC1 in the regulation of G2/M. J Biol Chem. 2009;284:8241-6 pubmed publisher
    Saccharomyces cerevisiae cells lacking ISC1 (inositol phosphosphingolipase C) exhibit sensitivity to genotoxic agents such as methyl methanesulfonate and hydroxyurea (HU)...
  6. Almeida T, Marques M, Mojzita D, Amorim M, Silva R, Almeida B, et al. Isc1p plays a key role in hydrogen peroxide resistance and chronological lifespan through modulation of iron levels and apoptosis. Mol Biol Cell. 2008;19:865-76 pubmed
    ..These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis. ..
  7. Tabuchi M, Audhya A, Parsons A, Boone C, Emr S. The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation. Mol Cell Biol. 2006;26:5861-75 pubmed
    ..Additionally, we identify Isc1, an inositol phosphosphingolipid phospholipase C, as an additional target of Slm1 and Slm2 negative regulation...
  8. Vaena De Avalos S, Okamoto Y, Hannun Y. Activation and localization of inositol phosphosphingolipid phospholipase C, Isc1p, to the mitochondria during growth of Saccharomyces cerevisiae. J Biol Chem. 2004;279:11537-45 pubmed
    ..cerevisiae, Isc1p; however, little is known about its regulation or physiologic function. Deletion of ISC1 in S...
  9. Kitagaki H, Cowart L, Matmati N, Vaena De Avalos S, Novgorodov S, Zeidan Y, et al. Isc1 regulates sphingolipid metabolism in yeast mitochondria. Biochim Biophys Acta. 2007;1768:2849-61 pubmed
    ..This study provides a first insight into the specific composition of ceramides in mitochondria. ..
  10. Teixeira V, Medeiros T, Vilaça R, Pereira A, Chaves S, Côrte Real M, et al. Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells. Cell Signal. 2015;27:1840-9 pubmed publisher
    ..Here, we show that isc1Δ cells display hyperactivation of mitophagy that is suppressed by downregulating Sit4p, Hog1p or the TORC1-..
  11. Cowart L, Okamoto Y, Lu X, Hannun Y. Distinct roles for de novo versus hydrolytic pathways of sphingolipid biosynthesis in Saccharomyces cerevisiae. Biochem J. 2006;393:733-40 pubmed
    ..Ceramide production was measured at normal and increased temperature in an ISC1 deletion and its parental strain (ISC1 being the gene that codes for Isc1p)...
  12. Betz C, Zajonc D, Moll M, Schweizer E. ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiae. Eur J Biochem. 2002;269:4033-9 pubmed
    ..Here, we report that the ISC1-encoded phosphosphingolipid-specific phospholipase C appears to be involved in stimulation of ENA1 expression and, ..