LKB1-AMPK Axis Negatively Regulates Ferroptosis by Inhibiting Fatty Acid Synthesis

Li, Changzhi; Dong, Xuan; Du, Wenjing; Shi, Xiaoxuan; Chen, Kangjie; Zhang, Wei; Gao, Minghui

doi:10.2139/ssrn.3499746

Cited by 16 publications

(19 citation statements)

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“…The depletion of LKB1 also can sensitize mouse embryonic fibroblasts to lipid hydroperoxidation and ferroptosis. 28 Long-chain fatty acids are mainly obtained from the diet and are named PUFA when they include more than two double bonds. 29 PUFAs are components of the cell membrane and regulate several biological functions, including inflammation, immunity, synaptic plasticity, and cellular growth.…”

Section: Regulation Of Ferroptosismentioning

confidence: 99%

Ferroptosis: mechanisms and links with diseases

Yan

Zou

Tuo

et al. 2021

Sig Transduct Target Ther

684

477

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Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer’s disease and Parkinson’s disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.

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Section: Regulation Of Ferroptosismentioning

confidence: 99%

Ferroptosis: mechanisms and links with diseases

Yan

Zou

Tuo

et al. 2021

Sig Transduct Target Ther

684

477

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“…In addition, RT can repress SLC7A11 expression in an ATM-dependent manner to further promote ferroptosis or upregulate SLC7A11 expression as an adaptive response for ferroptosis protection, depending on the context. Ferroptosis, radiotherapy, and combination strategies activity, thereby promoting ferroptosis , while energy stress-induced AMPK activation was recently shown to inhibit ferroptosis by restraining PUFA-PL biosynthesis (Lee et al, 2020;Li et al, 2020). The exact role of AMPK in RT-induced ferroptosis therefore remains to be examined.…”

Section: Other Potential Mechanismsmentioning

confidence: 99%

Ferroptosis, radiotherapy, and combination therapeutic strategies

et al. 2021

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Ferroptosis, an iron-dependent form of regulated cell death driven by peroxidative damages of polyunsaturated-fatty-acid-containing phospholipids in cellular membranes, has recently been revealed to play an important role in radiotherapy-induced cell death and tumor suppression, and to mediate the synergy between radiotherapy and immunotherapy. In this review, we summarize known as well as putative mechanisms underlying the crosstalk between radiotherapy and ferroptosis, discuss the interactions between ferroptosis and other forms of regulated cell death induced by radiotherapy, and explore combination therapeutic strategies targeting ferroptosis in radiotherapy and immunotherapy. This review will provide important frameworks for future investigations of ferroptosis in cancer therapy.

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“…Here we highlight a few additional unanswered questions for further studies in this emerging research area. Other signaling molecules, such as ACSL4 and AMP-activated protein kinase (AMPK), have been linked to both mTORC1 and ferroptosis, [6,[85][86][87][88][89] raising the question of whether ACSL4 or AMPK is also involved in the cross-talks between mTORC1 and ferroptosis. In addition, both mTORC1 and ferroptosis have been linked with immune system functions; [31,[90][91][92] therefore, it will be interesting to further understand the effects of mTOR inhibitors in combination with FINs on tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

mTORC1 and ferroptosis: Regulatory mechanisms and therapeutic potential

Lei

Gan

2021

BioEssays

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Ferroptosis, a form of regulated cell death triggered by lipid hydroperoxide accumulation, has an important role in a variety of diseases and pathological conditions, such as cancer. Targeting ferroptosis is emerging as a promising means of therapeutic intervention in cancer treatment. Polyunsaturated fatty acids, reactive oxygen species, and labile iron constitute the major underlying triggers for ferroptosis. Other regulators of ferroptosis have also been discovered recently, among them the mechanistic target of rapamycin complex 1 (mTORC1), a central controller of cell growth and metabolism.Inhibitors of mTORC1 have been used in treating diverse diseases, including cancer. In this review, we discuss recent findings linking mTORC1 to ferroptosis, dissect mechanisms underlying the establishment of mTORC1 as a key ferroptosis modulator, and highlight the potential of co-targeting mTORC1 and ferroptosis in cancer treatment. This review will provide valuable insights for future investigations of ferroptosis and mTORC1 in fundamental biology and cancer therapy.

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LKB1-AMPK Axis Negatively Regulates Ferroptosis by Inhibiting Fatty Acid Synthesis

Cited by 16 publications

References 0 publications

Ferroptosis: mechanisms and links with diseases

Ferroptosis: mechanisms and links with diseases

Ferroptosis, radiotherapy, and combination therapeutic strategies

mTORC1 and ferroptosis: Regulatory mechanisms and therapeutic potential

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