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

Crystal McGee,

Tirthankar Bandyopadhyay,

Cailin N McCracken

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 108131 - 108131

Published: Dec. 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.

Language: Английский

Mitochondriale und zytosolische Systeme der Eisen-Schwefel-Proteinbiogenese DOI Creative Commons
Roland Lill

BIOspektrum, Journal Year: 2025, Volume and Issue: 31(1), P. 18 - 22

Published: Feb. 1, 2025

Language: Английский

Citations

0
Control of Replication Stress Response by Cytosolic Fe-S Cluster Assembly (CIA) Machinery DOI Creative Commons
Chiara Frigerio, Michela Galli,

Stefano Castelli

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 442 - 442

Published: March 16, 2025

Accurate DNA replication is essential for the maintenance of genome stability and generation healthy offspring. When challenged, signals accumulate at blocked forks that elicit a multifaceted cellular response, orchestrating replication, repair cell cycle progression. This stress response promotes recovery maintaining chromosome integrity preventing mutations. Defects in this are linked to heightened genetic instability, which contributes tumorigenesis disorders. Iron–sulfur (Fe-S) clusters emerging as important cofactors supporting stress. These assembled delivered target proteins function cytosol nucleus via conserved cytosolic Fe-S cluster assembly (CIA) machinery CIA targeting complex. review summarizes recent advances understanding structure yeast mammals, emphasizing critical role response.

Language: Английский

Citations

0
Proteomic strategies to interrogate the Fe-S proteome DOI
Daniel W. Bak, Eranthie Weerapana

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(7), P. 119791 - 119791

Published: June 25, 2024

Language: Английский

Citations

2
Cysteine Import via the High Affinity Glutathione Transporter Hgt1 Rescues Glutathione Auxotrophy in Yeast DOI Creative Commons

Crystal McGee,

Tirthankar Bandyopadhyay,

Cailin N McCracken

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 108131 - 108131

Published: Dec. 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.

Language: Английский

Citations

0