RSL3 induced autophagic death in glioma cells via causing glycolysis dysfunction

Wang, Xuanzhong; Lu, Shan; He, Chuan; Wang, Chongcheng; Wang, Lei; Piao, Meihua; Chi, Guangfan; Luo, Yan; Ge, Pengfei

doi:10.1016/j.bbrc.2019.08.096

Cited by 64 publications

(56 citation statements)

References 27 publications

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“…Many ferroptosis inducers were found to increase autophagy and to impair lysosomal functionality that may contribute to the cell death [35]. Since both compounds used in the study showed to increase overall level of autophagy [20,22,[36][37][38], we verified if the NCOA4 knockingout could affect autophagy during ferroptosis pathway. The cells were treated as above for 8 h and analyzed for the level of LC3B protein, a member of LC3 family (microtubule-associated protein 1 light chain 3, known also as MAP1LC3), involved in autophagy, which is required for the recruitment of cargo-receptor complex, expansion of autophagosome membrane and fusion with lysosome [39].…”

Section: Ferritin Is Differently Modulated By Erastin and Rsl3mentioning

confidence: 78%

NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells

Gryzik

Asperti

Denardo

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

100

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Ferroptosis is a regulated cell death characterized by a lethal accumulation of lipid peroxides due to an increase of intracellular iron and a decrease of antioxidant capacity. The reduction of antioxidant activity is obtained by using chemical agents, such as erastin and RSL3, the first one inhibiting the transmembrane cystine-glutamate antiporter causing a cysteine and glutathione depletion and the second one inactivating directly the glutathione peroxidase 4 (GPX4) respectively. The role of iron and its related proteins in supporting the formation of lipid peroxides, is not completely understood hence to try to shed light on it we generated HeLa clones with altered ferritinophagy, the ferritin degradation process, by knocking-out or overexpressing Nuclear Receptor Coactivator 4 (NCOA4), the ferritin autophagic cargo-receptor. NCOA4 deficiency abolished ferritinophagy increasing ferritin level and making the cells more resistant to erastin, but unexpectedly more sensitive to RSL3. Interestingly, we found that erastin promoted ferritinophagy in HeLa cells expressing NCOA4, increasing the free iron, lipid peroxidation and the sensitivity to ferroptosis. In contrast, RSL3 did not modulate ferritinophagy, while NCOA4 overexpression delayed RSL3-induced cell death suggesting that RSL3 mechanism of action is independent of ferritin degradation process. Therefore, the ferritin-iron release in the execution of ferroptosis seems to depend on the inducing compound, its target and downstream pathway of cell death activation.

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Section: Ferritin Is Differently Modulated By Erastin and Rsl3mentioning

confidence: 78%

NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells

Gryzik

Asperti

Denardo

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

100

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“…It is known that GPX4 is an antioxidant peroxidase that directly reduces phospholipid hydroperoxide, and that inhibition of GPX4 results in accumulation of lipid ROS in cells (Brigelius-Flohé et al, 2013). In addition, it has been reported that some GPX4 inhibitors induce autophagy as confirmed by LC3 puncta formation and the conversion of LC3-I to LC3-II form (Hou et al, 2016;Wang et al, 2019). As previously reported, the amount of LC3 puncta and LC3-II form correlates with the quantity of autophagosomes (Mizushima et al, 2010).…”

Section: Cnp Inhibits Gpx4 Activity and Causes The Accumulation Of Lipid Ros In U-2 Os Cellsmentioning

confidence: 57%

Thermal Proteome Profiling Reveals Glutathione Peroxidase 4 as the Target of the Autophagy Inducer Conophylline

et al. 2021

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Jun N-terminal kinase; LC3, microtubule associated protein 1 light chain 3; LC-MS/MS, liquid chromatography-tandem mass spectrometry; mTOR, mammalian target of rapamycin; PBS, phosphate-buffered saline; p70S6K, p70 S6 kinase; RFP, red fluorescent protein TagRFP; ROS, reactive oxygen species; qRT-PCR, quantitative reverse transcription polymerase chain reaction; RPS6, S6 ribosomal protein; siRNA, small interference RNA; Tm, melting temperature; TPP, thermal proteome profiling; TR, temperature range.

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“…Moreover, supplement of pyruvate prevented RSL3-induced cell death, which indicated that glycolysis dysfunction could induce autophagic cell death in glioma cells. 35 Ji Hye Kim et al demonstrated that EGFR mutation-mediated enhancement of glycolysis sustains EGFR stability and is critical to EGFR-mutant NSCLC survival. Glucose metabolism inhibition is able to overcome T790M-mediated resistance because inhibition of glucose-derived ATP production could result in ROS-mediated c-Jun N-terminal kinase (JNK) activation, leading to autophagy-mediated degradation of EGFR.…”

Section: Glycolysis Regulates Autophagy During Tumor Growthmentioning

confidence: 99%

Regulation of Autophagy by Glycolysis in Cancer

Chu

Chang

Lü

et al. 2020

CMAR

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Autophagy is a critical cellular process that generally protects cells and organisms from harsh environment, including limitations in adenosine triphosphate (ATP) availability or a lack of essential nutrients. Metabolic reprogramming, a hallmark of cancer, has recently gained interest in the area of cancer therapy. It is well known that cancer cells prefer to utilize glycolysis rather than oxidative phosphorylation (OXPHOS) as their major energy source to rapidly generate ATP even in aerobic environment called the Warburg effect. Both autophagy and glycolysis play essential roles in pathological processes of cancer. A mechanism of metabolic changes to drive tumor progression is its ability to regulate autophagy. This review will elucidate the role and the mechanism of glycolysis in regulating autophagy during tumor growth. Indeed, understanding how glycolysis can modulate cellular autophagy will enable more effective combinatorial therapeutic strategies.

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RSL3 induced autophagic death in glioma cells via causing glycolysis dysfunction

Cited by 64 publications

References 27 publications

NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells

NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells

Thermal Proteome Profiling Reveals Glutathione Peroxidase 4 as the Target of the Autophagy Inducer Conophylline

Regulation of Autophagy by Glycolysis in Cancer

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