The yeast Magmas ortholog Pam16 has an essential function in fermentative growth that involves sphingolipid metabolism

Mary K. Short, Joshua P. Hallett, Krisztina Tar, Thomas Dange, Marion Schmidt, Robyn D. Moir, Ian M. Willis, Paul T. Jubinsky

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Magmas is a growth factor responsive gene encoding an essential mitochondrial protein in mammalian cells. Pam16, the Magmas ortholog in Saccharomyces cerevisiae, is a component of the presequence translocase-associated motor. A temperature-sensitive allele (pam16-I61N) was used to query an array of non-essential gene-deletion strains for synthetic genetic interactions. The pam16-I61N mutation at ambient temperature caused synthetic lethal or sick phenotypes with genes involved in lipid metabolism, perixosome synthesis, histone deacetylation and mitochondrial protein import. The gene deletion array was also screened for suppressors of the pam16-I61N growth defect to identify compensatory pathways. Five suppressor genes were identified (SUR4, ISC1, IPT1, SKN1, and FEN1) and all are involved in sphingolipid metabolism. pam16-I61N cells cultured in glucose at non-permissive temperatures resulted in rapid growth inhibition and G1 cell cycle arrest, but cell viability was maintained. Altered mitochondria morphology, reduced peroxisome induction in glycerol/ethanol and oleate, and changes in the levels of several sphingolipids including C18 alpha-hydroxy-phytoceramide, were also observed in the temperature sensitive strain. Deletion of SUR4, the strongest suppressor, reversed the temperature sensitive fermentative growth defect, the morphological changes and the elevated levels of C18 alpha-hydroxy phytoceramide in pam16-I61N. Deletion of the other four suppressor genes had similar effects on C18 alpha-hydroxy-phytoceramide levels and restored proliferation to the pam16-I61N strain. In addition, pam16-I61N inhibited respiratory growth, likely by reducing cardiolipin, which is essential for mitochondrial function. Our results suggest that the pleiotropic effects caused by impaired Pam16/Magmas function are mediated in part by changes in lipid metabolism.

Original languageEnglish (US)
Article numbere39428
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 10 2012

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sphingolipids
Sphingolipids
Metabolism
Yeast
Genes
Yeasts
suppressor genes
yeasts
Temperature
metabolism
gene deletion
Suppressor Genes
Growth
lipid metabolism
Mitochondrial Proteins
Cells
Gene Deletion
temperature
Lipid Metabolism
cardiolipins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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The yeast Magmas ortholog Pam16 has an essential function in fermentative growth that involves sphingolipid metabolism. / Short, Mary K.; Hallett, Joshua P.; Tar, Krisztina; Dange, Thomas; Schmidt, Marion; Moir, Robyn D.; Willis, Ian M.; Jubinsky, Paul T.

In: PLoS One, Vol. 7, No. 7, e39428, 10.07.2012.

Research output: Contribution to journalArticle

Short, Mary K. ; Hallett, Joshua P. ; Tar, Krisztina ; Dange, Thomas ; Schmidt, Marion ; Moir, Robyn D. ; Willis, Ian M. ; Jubinsky, Paul T. / The yeast Magmas ortholog Pam16 has an essential function in fermentative growth that involves sphingolipid metabolism. In: PLoS One. 2012 ; Vol. 7, No. 7.
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abstract = "Magmas is a growth factor responsive gene encoding an essential mitochondrial protein in mammalian cells. Pam16, the Magmas ortholog in Saccharomyces cerevisiae, is a component of the presequence translocase-associated motor. A temperature-sensitive allele (pam16-I61N) was used to query an array of non-essential gene-deletion strains for synthetic genetic interactions. The pam16-I61N mutation at ambient temperature caused synthetic lethal or sick phenotypes with genes involved in lipid metabolism, perixosome synthesis, histone deacetylation and mitochondrial protein import. The gene deletion array was also screened for suppressors of the pam16-I61N growth defect to identify compensatory pathways. Five suppressor genes were identified (SUR4, ISC1, IPT1, SKN1, and FEN1) and all are involved in sphingolipid metabolism. pam16-I61N cells cultured in glucose at non-permissive temperatures resulted in rapid growth inhibition and G1 cell cycle arrest, but cell viability was maintained. Altered mitochondria morphology, reduced peroxisome induction in glycerol/ethanol and oleate, and changes in the levels of several sphingolipids including C18 alpha-hydroxy-phytoceramide, were also observed in the temperature sensitive strain. Deletion of SUR4, the strongest suppressor, reversed the temperature sensitive fermentative growth defect, the morphological changes and the elevated levels of C18 alpha-hydroxy phytoceramide in pam16-I61N. Deletion of the other four suppressor genes had similar effects on C18 alpha-hydroxy-phytoceramide levels and restored proliferation to the pam16-I61N strain. In addition, pam16-I61N inhibited respiratory growth, likely by reducing cardiolipin, which is essential for mitochondrial function. Our results suggest that the pleiotropic effects caused by impaired Pam16/Magmas function are mediated in part by changes in lipid metabolism.",
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