Phosphorylation of eIF2α suppresses the impairment of GSH/NADPH homeostasis and mitigates the activation of cell death pathways, including ferroptosis, during ER stress DOI Open Access
Lê Thị Thu Hiền, Yong Hwan Kim, Mi Jeong Kim

и другие.

Molecules and Cells, Год журнала: 2025, Номер unknown, С. 100210 - 100210

Опубликована: Март 1, 2025

eIF2α phosphorylation helps maintain cellular homeostasis and overcome endoplasmic reticulum (ER) stress through transcriptional translational reprogramming. This study aims to elucidate the regulation of glutathione (GSH) NADPH its impact on cell death during ER stress. phosphorylation-deficient (A/A) cells exhibited decreased expression multiple genes involved in GSH synthesis production, leading an exacerbated depletion both mitochondrial GSH, as well NADPH, Impaired resulted from deficient ATF4 and/or dependent factor, Nrf2, which are key transcription factors antioxidant response In contrast, exacerbation may primarily be attributed dysregulated serine-driven one-carbon metabolism pathway genes, regulated by unidentified phosphorylation-dependent mechanism Moreover, phosphorylation-ATF4 axis was responsible for upregulation ferroptosis-inhibiting downregulation ferroptosis-activating upon Therefore, strongly induced ferroptosis A/A cells, significantly inhibited treatments with cell-permeable inhibitor ferrostatin-1 (Fer-1). overexpression suppressed impairment promoting downstream target genes. Consequently, mitigated apoptosis Our findings underscore importance maintaining GSH/NADPH inhibiting target(s)-mediated reprogramming

Язык: Английский

Phosphorylation of eIF2α suppresses the impairment of GSH/NADPH homeostasis and mitigates the activation of cell death pathways, including ferroptosis, during ER stress DOI Open Access
Lê Thị Thu Hiền, Yong Hwan Kim, Mi Jeong Kim

и другие.

Molecules and Cells, Год журнала: 2025, Номер unknown, С. 100210 - 100210

Опубликована: Март 1, 2025

eIF2α phosphorylation helps maintain cellular homeostasis and overcome endoplasmic reticulum (ER) stress through transcriptional translational reprogramming. This study aims to elucidate the regulation of glutathione (GSH) NADPH its impact on cell death during ER stress. phosphorylation-deficient (A/A) cells exhibited decreased expression multiple genes involved in GSH synthesis production, leading an exacerbated depletion both mitochondrial GSH, as well NADPH, Impaired resulted from deficient ATF4 and/or dependent factor, Nrf2, which are key transcription factors antioxidant response In contrast, exacerbation may primarily be attributed dysregulated serine-driven one-carbon metabolism pathway genes, regulated by unidentified phosphorylation-dependent mechanism Moreover, phosphorylation-ATF4 axis was responsible for upregulation ferroptosis-inhibiting downregulation ferroptosis-activating upon Therefore, strongly induced ferroptosis A/A cells, significantly inhibited treatments with cell-permeable inhibitor ferrostatin-1 (Fer-1). overexpression suppressed impairment promoting downstream target genes. Consequently, mitigated apoptosis Our findings underscore importance maintaining GSH/NADPH inhibiting target(s)-mediated reprogramming

Язык: Английский

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