Elevation of cellular Mg2+ levels by the Mg2+ transporter, Alr1, supports growth of polyamine-deficient Saccharomyces cerevisiae cells

Ashleigh S. Hanner, Matthew Dunworth, Robert A. Casero, Colin W. MacDiarmid, Myung Hee Park

Research output: Contribution to journalArticlepeer-review

Abstract

The polyamines putrescine, spermidine, and spermine are required for normal eukaryotic cellular functions. However, the minimum requirement for polyamines varies widely, ranging from very high concentrations (mM) in mammalian cells to extremely low in the yeast Saccharomyces cerevisiae. Yeast strains deficient in polyamine biosynthesis (spe1δ, lacking ornithine decarboxylase, and spe2δ, lacking SAM decarboxylase) require externally supplied polyamines, but supplementation with as little as 108 M spermidine restores their growth. Here, we report that culturing a spe1δ mutant or a spe2δ mutant in a standard polyamine-free minimal medium (SDC) leads to marked increases in cellular Mg2 content. To determine which yeast Mg2 transporter mediated this increase, we generated mutant strains with a deletion of SPE1 or SPE2 combined with a deletion of one of the three Mg2 transporter genes, ALR1, ALR2, and MNR2, known to maintain cytosolic Mg2 concentration. Neither Alr2 nor Mnr2 was required for increased Mg2 accumulation, as all four double mutants (spe1δ alr2δ, spe2δ alr2δ, spe1δ mnr2δ, and spe2δ mnr2δ) exhibited significant Mg2 accumulation upon polyamine depletion. In contrast, a spe2δ alr1δ double mutant cultured in SDC exhibited little increase in Mg2 content and displayed severe growth defects compared with single mutants alr1δ and spe2δ under polyamine-deficient conditions. These findings indicate that Alr1 is required for the up-regulation of the Mg2 content in polyamine-depleted cells and suggest that elevated Mg2 can support growth of polyamine-deficient S. cerevisiae mutants. Upregulation of cellular polyamine content in a Mg2-deficient alr1δ mutant provided further evidence for a cross-talk between Mg2 and polyamine metabolism.

Original languageEnglish (US)
Pages (from-to)17131-17142
Number of pages12
JournalJournal of Biological Chemistry
Volume294
Issue number45
DOIs
StatePublished - Nov 8 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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