TY - JOUR
T1 - Elevation of cellular Mg2+ levels by the Mg2+ transporter, Alr1, supports growth of polyamine-deficient Saccharomyces cerevisiae cells
AU - Hanner, Ashleigh S.
AU - Dunworth, Matthew
AU - Casero, Robert A.
AU - MacDiarmid, Colin W.
AU - Park, Myung Hee
N1 - Publisher Copyright:
© 2019 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved.
PY - 2019/11/8
Y1 - 2019/11/8
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.RA119.009705
DO - 10.1074/jbc.RA119.009705
M3 - Article
C2 - 31548311
AN - SCOPUS:85074736796
SN - 0021-9258
VL - 294
SP - 17131
EP - 17142
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -