NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism DOI Creative Commons
Jiao Liu, Hu Tang, Fangquan Chen

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 28, 2024

Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial copper accumulation and proteotoxic stress. Here, we provide the first evidence that glutathione (GSH), major non-protein thiol in cells, acts as cuproptosis inhibitor pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, GSH inhibits chelating copper, contrasting its role blocking ferroptosis inhibiting lipid peroxidation. The classical inducer, ES-Cu (elesclomol plus copper), increases protein stability transcription factor NFE2L2 (also known NRF2), leading to upregulation gene expression glutamate-cysteine ligase modifier subunit (GCLM) catalytic (GCLC). GCLM GCLC are rate-limiting enzymes synthesis, increased transported into mitochondria via solute carrier family 25 member 39 (SLC25A39) transporter. Consequently, genetic inhibition NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression culture mouse models. These findings not only reveal distinct mechanisms ferroptosis, but also suggest potential combination strategy suppress PDAC growth.

Language: Английский

Ferroptosis crosstalk in anti-tumor immunotherapy: molecular mechanisms, tumor microenvironment, application prospects DOI
Y. F. Lu,

Xiao‐Ting Xie,

Lianxiang Luo

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(11-12), P. 1914 - 1943

Published: July 15, 2024

Language: Английский

Citations

7
The complex interplay between ferroptosis and atherosclerosis DOI Open Access

Mao Zhang,

Jianping Li, Wei Hu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117183 - 117183

Published: July 30, 2024

Atherosclerosis, characterized by the accumulation of plaque within arterial walls, is an intricate cardiovascular disease that often results in severe health issues. Recent studies have emphasized importance ferroptosis, a controlled type cell death dependent on iron, as critical factor this state. Ferroptosis, distinguished its reliance iron and lipid hydroperoxides, offers unique insight into pathology atherosclerotic lesions. This summary encapsulates current knowledge role ferroptosis plays onset progression atherosclerosis. It explores molecular processes through which peroxidation metabolism contribute to development atheromatous plaques evaluates possibility utilizing novel treatment approach for By illuminating relationship between ferroptosis-related atherosclerosis, review paves way future clinical applications personalized medicine approaches aimed at alleviating effects

Language: Английский

Citations

5
SLC7A11 protects luminal A breast cancer cells against ferroptosis induced by CDK4/6 inhibitors DOI Creative Commons

Yingshu Cui,

Yi Li, Yuanyuan Xu

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103304 - 103304

Published: Aug. 10, 2024

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) can significantly extend tumor response in patients with metastatic luminal A breast cancer, yet intrinsic acquired resistance remains a prevalent issue. Understanding the molecular features of CDK4/6 inhibitor sensitivity potential efficacy their combination novel targeted cell death inducers may lead to improved patient outcomes. Herein, we demonstrate that ferroptosis, form regulated driven by iron-dependent phospholipid peroxidation, partly underpins inhibitors. Mechanistically, downregulate cystine transporter SLC7A11 inhibiting SP1 binding promoter region. Furthermore, is identified as critical for cancer Both genetic pharmacological inhibition or enhances synergistically inhibits growth when combined vitro vivo. Our data highlight targeting inhibitors, supporting further investigation therapy cancer.

Language: Английский

Citations

5
The solute carrier transporters (SLCs) family in nutrient metabolism and ferroptosis DOI Creative Commons

Lili Sun,

Haiyan He,

Wei Li

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 2, 2024

Abstract Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due the accumulation peroxides in response various stimuli, such as high levels iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial regulating ferroptosis. The solute carrier transporters (SLCs) family, known “metabolic gating” cells, responsible for transporting intracellular nutrients metabolites. Recent studies have highlighted significant role SLCs family members ferroptosis controlling transport nutrients. Here, we summarized function mechanism regulated ion, control nutrients, multiple signaling pathways, with focus on SLC–related that primarily five components: glucose, trace metal other ion. Furthermore, potential clinical applications targeting inducers diseases, including tumors, discussed. Overall, this paper delves into roles ferroptosis, aiming enhance our understanding regulatory mechanisms identify new therapeutic targets applications.

Language: Английский

Citations

5
NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism DOI Creative Commons
Jiao Liu, Hu Tang, Fangquan Chen

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 28, 2024

Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial copper accumulation and proteotoxic stress. Here, we provide the first evidence that glutathione (GSH), major non-protein thiol in cells, acts as cuproptosis inhibitor pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, GSH inhibits chelating copper, contrasting its role blocking ferroptosis inhibiting lipid peroxidation. The classical inducer, ES-Cu (elesclomol plus copper), increases protein stability transcription factor NFE2L2 (also known NRF2), leading to upregulation gene expression glutamate-cysteine ligase modifier subunit (GCLM) catalytic (GCLC). GCLM GCLC are rate-limiting enzymes synthesis, increased transported into mitochondria via solute carrier family 25 member 39 (SLC25A39) transporter. Consequently, genetic inhibition NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression culture mouse models. These findings not only reveal distinct mechanisms ferroptosis, but also suggest potential combination strategy suppress PDAC growth.

Language: Английский

Citations

5