Direct Interaction of Saccharomyces Cerevisiae Faa1p with the Omi/HtrA Protease Orthologue Ynm3p Alters Lipid Homeostasis

Overview

Journal Mol Genet Genomics

Specialty Genetics

Date 2006 Feb 14

PMID 16470384

Citations 4

Authors

Fumin Tong

Paul N Black

Lori Bivins

Steven Quackenbush

Vlasta Ctrnacta

Concetta C DiRusso

Affiliations

Soon will be listed here.

Abstract

In yeast, long chain acyl-CoA synthetase (ACSL) activity is required for fatty acid uptake, metabolism and fatty acid-dependent transcriptional control. The major ACSL contributing these functions is Faa1p. In a yeast two-hybrid screen, the Omi/HtrA serine protease family orthologue Ynm3p (YNL123w) was identified as a specific interactor with Faa1p. Interaction of Ynm3p and Faa1p was confirmed by co-immunoprecipitation. Disruption of the YNM3 gene encoding Ynm3p resulted in increased fatty acid uptake, triglyceride accumulation and reduced expression of the fatty acid-responsive OLE1 gene encoding the essential Delta(9)-acyl-CoA desaturase. These changes were linked with increased Faa1p and Faa4p ACSL activities. We propose that Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity. Additional strain-specific phenotypes associated with deletion of YNM3 included inability to grow on non-fermentable carbon sources and altered cellular morphology.

Citing Articles

Lipids and cell death in yeast.

Eisenberg T, Buttner S FEMS Yeast Res. 2013; 14(1):179-97.

PMID: 24119111 PMC: 4255311. DOI: 10.1111/1567-1364.12105.

A new principle of oligomerization of plant DEG7 protease based on interactions of degenerated protease domains.

Schuhmann H, Mogg U, Adamska I Biochem J. 2011; 435(1):167-74.

PMID: 21247409 PMC: 3194040. DOI: 10.1042/BJ20101613.

The yeast HtrA orthologue Ynm3 is a protease with chaperone activity that aids survival under heat stress.

Padmanabhan N, Fichtner L, Dickmanns A, Ficner R, Schulz J, Braus G Mol Biol Cell. 2008; 20(1):68-77.

PMID: 18946088 PMC: 2613113. DOI: 10.1091/mbc.e08-02-0178.

A genomewide functional network for the laboratory mouse.

Guan Y, Myers C, Lu R, Lemischka I, Bult C, Troyanskaya O PLoS Comput Biol. 2008; 4(9):e1000165.

PMID: 18818725 PMC: 2527685. DOI: 10.1371/journal.pcbi.1000165.

References

Unger R . Lipotoxic diseases. Annu Rev Med. 2002; 53:319-36. DOI: 10.1146/annurev.med.53.082901.104057. View

Zhang S, Skalsky Y, Garfinkel D . MGA2 or SPT23 is required for transcription of the delta9 fatty acid desaturase gene, OLE1, and nuclear membrane integrity in Saccharomyces cerevisiae. Genetics. 1999; 151(2):473-83. PMC: 1460504. DOI: 10.1093/genetics/151.2.473. View

Faergeman N, DiRusso C, Elberger A, Knudsen J, Black P . Disruption of the Saccharomyces cerevisiae homologue to the murine fatty acid transport protein impairs uptake and growth on long-chain fatty acids. J Biol Chem. 1997; 272(13):8531-8. DOI: 10.1074/jbc.272.13.8531. View

Johnson D, Knoll L, Levin D, Gordon J . Saccharomyces cerevisiae contains four fatty acid activation (FAA) genes: an assessment of their role in regulating protein N-myristoylation and cellular lipid metabolism. J Cell Biol. 1994; 127(3):751-62. PMC: 2120220. DOI: 10.1083/jcb.127.3.751. View

Eisler H, Frohlich K, Heidenreich E . Starvation for an essential amino acid induces apoptosis and oxidative stress in yeast. Exp Cell Res. 2004; 300(2):345-53. DOI: 10.1016/j.yexcr.2004.07.025. View

Madeo F, Frohlich E, Ligr M, Grey M, Sigrist S, Wolf D . Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol. 1999; 145(4):757-67. PMC: 2133192. DOI: 10.1083/jcb.145.4.757. View

Duronio R, Knoll L, Gordon J . Isolation of a Saccharomyces cerevisiae long chain fatty acyl:CoA synthetase gene (FAA1) and assessment of its role in protein N-myristoylation. J Cell Biol. 1992; 117(3):515-29. PMC: 2289438. DOI: 10.1083/jcb.117.3.515. View

Hanes S, Brent R . DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9. Cell. 1989; 57(7):1275-83. DOI: 10.1016/0092-8674(89)90063-9. View

Madeo F, Frohlich E, Frohlich K . A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol. 1997; 139(3):729-34. PMC: 2141703. DOI: 10.1083/jcb.139.3.729. View

10.

Unger R, Orci L . Lipotoxic diseases of nonadipose tissues in obesity. Int J Obes Relat Metab Disord. 2000; 24 Suppl 4:S28-32. DOI: 10.1038/sj.ijo.0801498. View

11.

Choi J, Stukey J, Hwang S, Martin C . Regulatory elements that control transcription activation and unsaturated fatty acid-mediated repression of the Saccharomyces cerevisiae OLE1 gene. J Biol Chem. 1996; 271(7):3581-9. DOI: 10.1074/jbc.271.7.3581. View

12.

Martins L, Morrison A, Klupsch K, Fedele V, Moisoi N, Teismann P . Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol Cell Biol. 2004; 24(22):9848-62. PMC: 525490. DOI: 10.1128/MCB.24.22.9848-9862.2004. View

13.

Golemis E, Serebriiskii I, Law S . The yeast two-hybrid system: criteria for detecting physiologically significant protein-protein interactions. Curr Issues Mol Biol. 2001; 1(1-2):31-45. View

14.

Zhang Q, Chieu H, Low C, Zhang S, Heng C, Yang H . Schizosaccharomyces pombe cells deficient in triacylglycerols synthesis undergo apoptosis upon entry into the stationary phase. J Biol Chem. 2003; 278(47):47145-55. DOI: 10.1074/jbc.M306998200. View

15.

Zou Z, Tong F, Faergeman N, Borsting C, Black P, DiRusso C . Vectorial acylation in Saccharomyces cerevisiae. Fat1p and fatty acyl-CoA synthetase are interacting components of a fatty acid import complex. J Biol Chem. 2003; 278(18):16414-22. DOI: 10.1074/jbc.M210557200. View

16.

Verhagen A, Silke J, Ekert P, Pakusch M, Kaufmann H, Connolly L . HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem. 2001; 277(1):445-54. DOI: 10.1074/jbc.M109891200. View

17.

Sikorski R, Hieter P . A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989; 122(1):19-27. PMC: 1203683. DOI: 10.1093/genetics/122.1.19. View

18.

Gietz R, Woods R . Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol. 2002; 350:87-96. DOI: 10.1016/s0076-6879(02)50957-5. View

19.

McHale M, Kroening K, Bernlohr D . Identification of a class of Saccharomyces cerevisiae mutants defective in fatty acid repression of gene transcription and analysis of the frm2 gene. Yeast. 1996; 12(4):319-31. DOI: 10.1002/(SICI)1097-0061(19960330)12:4%3C319::AID-YEA914%3E3.0.CO;2-#. View

20.

Li H, Black P, DiRusso C . A live-cell high-throughput screening assay for identification of fatty acid uptake inhibitors. Anal Biochem. 2004; 336(1):11-9. DOI: 10.1016/j.ab.2004.09.025. View