Integrated regulation of stress responses, autophagy and survival by altered intracellular iron stores

Wang, Yunyang; Wang, Mo; Liu, Yuying; Tao, Hui; Banerjee, Somesh; Srinivasan, Shanthi; Nemeth, Elizabeta; Czaja, Mark J.; He, Peijian

doi:10.1016/j.redox.2022.102407

Cited by 25 publications

(20 citation statements)

References 70 publications

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“…Interestingly, previous studies have shown that lysosomal Fe 2+ efflux caused by HIV-1gp120 led to ROS accumulation . Lysosomes are involved in ferritin degradation and may cause efflux of ferric ions from lysosomes after lysosomal membrane permeabilization . Consistent with this, we used LysoTracker green and Fe 2+ probe to colocalize lysosomal iron showing that sodium sulfite promoted lysosomal iron efflux and the administration of lysosomal iron ion chelator DFO alleviated sodium sulfite-induced ferroptosis.…”

Section: Discussionmentioning

confidence: 98%

“…Lysosomes occupy a central position in iron homeostasis and are the first organelles to receive extracellular iron input via the endocytic pathway . Lysosomes store iron and further mediate the cell death pathway by initiating lysosomal membrane permeabilization . A series of studies have shown that lysosomes were the executors of ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

“…12 Lysosomes store iron and further mediate the cell death pathway by initiating lysosomal membrane permeabilization. 45 A series of studies have shown that lysosomes were the executors of ferroptosis. Since lysosomes lack antioxidant enzymes, they are more susceptible to oxidative damage, resulting in lysosomal membrane permeabilization.…”

Section: ■ Discussionmentioning

confidence: 99%

“…47 Lysosomes are involved in ferritin degradation and may cause efflux of ferric ions from lysosomes after lysosomal membrane permeabilization. 45 Consistent with this, we used LysoTracker green and Fe 2+ probe to colocalize lysosomal iron showing that sodium sulfite promoted lysosomal iron efflux and the administration of lysosomal iron ion chelator DFO alleviated sodium sulfite-induced ferroptosis. Similarly, Panigrahi et al showed that enhanced oxidative stress induces lysosomal membrane permeabilization and lysosomal iron efflux to the cytoplasm, leading to cell death.…”

Section: ■ Discussionmentioning

confidence: 99%

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Sodium Sulfite-Triggered Hepatocyte Ferroptosis via mtROS/Lysosomal Membrane Permeabilization-Mediated Lysosome Iron Efflux

Liu,

Lu,

Chen

et al. 2023

J. Agric. Food Chem.

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Sodium sulfite is a widely used preservative in the food industry. Ferroptosis has been a newly discovered form of iron-dependent oxidative cell death in recent years. However, the potential connection between sodium sulfite and ferroptosis has not been explored. In our study, we observed the abnormal expression of ferroptosis marker protein in vivo, suggesting that sodium sulfite caused ferroptosis in vivo. Next, our study revealed that sodium sulfite caused the overproduction of mitochondrial reactive oxygen species (mtROS) in the AML-12 cells. It is well established that reactive oxygen species (ROS) can induce lysosomal membrane permeabilization. After lysosomal membrane permeabilization occurs, the outflow of Fe 2+ in lysosomes triggers the Fenton reaction and subsequently results in the increase of intracellular ROS level, which is closely related to ferroptosis. As speculated, acridine orange (AO) staining and LysoTracker red staining showed that sodium sulfite-induced lysosomal membrane permeabilization could be alleviated by mtROS scavenger TEMPO. In addition, TEMPO, lysosomal stabilizer mannose, and lysosomal iron chelator deferoxamine (DFO) inhibited sodium sulfite-induced ferroptosis. Overall, the results showed that sodium sulfite induced lysosomal iron efflux through the mtROS-lysosomal membrane permeabilization pathway and eventually led to ferroptosis. Our study might provide a new mechanism for the hepatotoxicity of sodium sulfite and a theoretical basis for the risk assessment of sodium sulfite as a food additive.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Sodium Sulfite-Triggered Hepatocyte Ferroptosis via mtROS/Lysosomal Membrane Permeabilization-Mediated Lysosome Iron Efflux

Liu,

Lu,

Chen

et al. 2023

J. Agric. Food Chem.

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“…Additionally, research has demonstrated that ATF6 also exerts inhibitory effects on gluconeogenesis. It has been shown that ATF6 modulates the activity of the key transcription factor cAMP response element-binding protein (CREB) by competing with the transcriptional coactivator transducer of regulated CREB activity 2 (TORC2), thereby suppressing gluconeogenesis in the mouse liver ( 117 ). The increase in ERS promotes the expression of ER quality control genes through association with ATF6α.…”

Section: Ers-mediated Inflammatory Cascadementioning

confidence: 99%

Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue

Ma,

Zhang,

Zhao

et al. 2024

Front. Immunol.

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Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

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Excess iron accumulation mediated senescence in diabetic kidney injury

Cheng,

Li,

Chen

et al. 2024

J Biochem & Molecular Tox

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Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high‐fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, β‐galactosidase staining, 5‐ethynyl‐2‐deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG‐treated cells caused increased LDH release from normal cells. Iron metabolism‐related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 μM) upregulated gamma‐H2A.X variant histone and increased the senescence markers in HG‐treated cells. The treatment of deferoxamine (0.5 μM) had the opposite effect. Compared to the non‐DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co‐localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.

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Integrated regulation of stress responses, autophagy and survival by altered intracellular iron stores

Cited by 25 publications

References 70 publications

Sodium Sulfite-Triggered Hepatocyte Ferroptosis via mtROS/Lysosomal Membrane Permeabilization-Mediated Lysosome Iron Efflux

Sodium Sulfite-Triggered Hepatocyte Ferroptosis via mtROS/Lysosomal Membrane Permeabilization-Mediated Lysosome Iron Efflux

Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue

Excess iron accumulation mediated senescence in diabetic kidney injury

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