Cysteine Import via the High Affinity Glutathione Transporter Hgt1 Rescues Glutathione Auxotrophy in Yeast DOI Creative Commons

Crystal McGee,

Tirthankar Bandyopadhyay,

Cailin N McCracken

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер unknown, С. 108131 - 108131

Опубликована: Дек. 1, 2024

Glutathione (GSH) is an abundant thiol-containing tripeptide that functions in redox homeostasis, protein folding, and iron metabolism. In Saccharomyces cerevisiae, GSH depletion leads to increased sensitivity oxidants other toxic compounds, disruption of Fe-S cluster biogenesis, eventually cell death. pools are supplied by intracellular biosynthesis import from the extracellular environment. Consequently, GSH-depleted growth media, deletion gene encoding first enzyme biosynthetic pathway (GSH1), lethal yeast. At extreme, overaccumulation via overexpression high affinity transporter Hgt1 also cells, leading reductive stress. Here we engineered a yeast strain combines GSH1 with HGT1 study cellular effects oscillating between deplete replete conditions. Surprisingly, find constitutive expression gsh1Δ cells rescues auxotrophy this strain. We show addition cysteine or derivatives media required for rescue. limitation causes overload due iron-sulfur (Fe-S) dependent regulates activity low sensing transcription factors Aft1 Aft2. Analysis regulation pathways reveals partially alleviates starvation-like response cells. Taken together, these results suggest facilitates allow limited biogenesis sustain absence GSH.

Язык: Английский

Cysteine Import via the High Affinity Glutathione Transporter Hgt1 Rescues Glutathione Auxotrophy in Yeast DOI Creative Commons

Crystal McGee,

Tirthankar Bandyopadhyay,

Cailin N McCracken

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер unknown, С. 108131 - 108131

Опубликована: Дек. 1, 2024

Glutathione (GSH) is an abundant thiol-containing tripeptide that functions in redox homeostasis, protein folding, and iron metabolism. In Saccharomyces cerevisiae, GSH depletion leads to increased sensitivity oxidants other toxic compounds, disruption of Fe-S cluster biogenesis, eventually cell death. pools are supplied by intracellular biosynthesis import from the extracellular environment. Consequently, GSH-depleted growth media, deletion gene encoding first enzyme biosynthetic pathway (GSH1), lethal yeast. At extreme, overaccumulation via overexpression high affinity transporter Hgt1 also cells, leading reductive stress. Here we engineered a yeast strain combines GSH1 with HGT1 study cellular effects oscillating between deplete replete conditions. Surprisingly, find constitutive expression gsh1Δ cells rescues auxotrophy this strain. We show addition cysteine or derivatives media required for rescue. limitation causes overload due iron-sulfur (Fe-S) dependent regulates activity low sensing transcription factors Aft1 Aft2. Analysis regulation pathways reveals partially alleviates starvation-like response cells. Taken together, these results suggest facilitates allow limited biogenesis sustain absence GSH.

Язык: Английский

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