Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases

Feng, Qi; Yang, Yang; Ren, Kai-Di; Qiao, Ye; Sun, Zhoutong; Pan, Shaokang; Liu, Fengxun; Liu, Yong; Huo, Jiandong; Li, Dongwei; Liu, Zhangsuo

doi:10.7150/ijbs.85674

Cited by 9 publications

(2 citation statements)

References 165 publications

(188 reference statements)

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“…Existing research suggests a bidirectional relationship between AKI and CKD, with AKI promoting CKD development, which, in turn, heightens susceptibility to AKI [ 141 ]. Besides AKI, the role of ferroptosis in various kidney diseases, including renal carcinoma, acute kidney injury, kidney fibrosis, and kidney inflammation, should not be overlooked [ 143 ]. Therefore, we believe that the role of ferroptosis in CKD is also substantial.…”

Section: Ferroptosis and Ckdmentioning

confidence: 99%

Role of ferroptosis in chronic kidney disease

Li,

Han,

Liu

et al. 2024

Cell Commun Signal

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Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment.

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Section: Ferroptosis and Ckdmentioning

confidence: 99%

Role of ferroptosis in chronic kidney disease

Li,

Han,

Liu

et al. 2024

Cell Commun Signal

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“…BH4 promotes the synthesis of CoQ10 by converting phenylalanine to tyrosine, thereby serving as a free radical-trapping antioxidant [ 116 ]. Additionally, GCH1, a rate-limiting enzyme synthesized by BH4, has the potential to suppress ferroptosis [ 117 ]. The expression of GCH1 induces lipid remodeling in cells, inhibiting ferroptosis by selectively preventing the consumption of PLs with two PUFA tails [ 25 ].…”

Section: Potential Mechanisms Of Gut Microbiota Interaction With Ferr...mentioning

confidence: 99%

Ferroptosis: a potential bridge linking gut microbiota and chronic kidney disease

Mao,

Gao,

Pan

et al. 2024

Cell Death Discov.

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Ferroptosis is a novel form of lipid peroxidation-driven, iron-dependent programmed cell death. Various metabolic pathways, including those involved in lipid and iron metabolism, contribute to ferroptosis regulation. The gut microbiota not only supplies nutrients and energy to the host, but also plays a crucial role in immune modulation and metabolic balance. In this review, we explore the metabolic pathways associated with ferroptosis and the impact of the gut microbiota on host metabolism. We subsequently summarize recent studies on the influence and regulation of ferroptosis by the gut microbiota and discuss potential mechanisms through which the gut microbiota affects ferroptosis. Additionally, we conduct a bibliometric analysis of the relationship between the gut microbiota and ferroptosis in the context of chronic kidney disease. This analysis can provide new insights into the current research status and future of ferroptosis and the gut microbiota.

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ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25‐mediated ubiquitination of ACSL3

Han,

Guo,

Kong

et al. 2024

Clinical & Translational Med

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BackgroundRenal ischaemia‒reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI). To date, effective therapies for delaying renal IRI and postponing patient survival remain absent. Ankyrin repeat domain 1 (ANKRD1) has been implicated in some pathophysiologic processes, but its role in renal IRI has not been explored.MethodsThe mouse model of IRI‐AKI and in vitro model were utilised to investigate the role of ANKRD1. Immunoprecipitation‐mass spectrometry was performed to identify potential ANKRD1‐interacting proteins. Protein‒protein interactions and protein ubiquitination were examined using immunoprecipitation and proximity ligation assay and immunoblotting, respectively. Cell viability, damage and lipid peroxidation were evaluated using biochemical and cellular techniques.ResultsFirst, we unveiled that ANKRD1 were significantly elevated in renal IRI models. Global knockdown of ANKRD1 in all cell types of mouse kidney by recombinant adeno‐associated virus (rAAV9)‐mitigated ischaemia/reperfusion‐induced renal damage and failure. Silencing ANKRD1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells exposed to hypoxia reoxygenation or hydrogen peroxide, while ANKRD1 overexpression had the opposite effect. Second, we discovered that ANKRD1's detrimental function during renal IRI involves promoting lipid peroxidation and ferroptosis by directly binding to and decreasing levels of acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3), a key protein in lipid metabolism. Furthermore, attenuating ACSL3 in vivo through pharmaceutical approach and in vitro via RNA interference mitigated the anti‐ferroptotic effect of ANKRD1 knockdown. Finally, we showed ANKRD1 facilitated post‐translational degradation of ACSL3 by modulating E3 ligase tripartite motif containing 25 (TRIM25) to catalyse K63‐linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis, exacerbating renal injury.ConclusionsOur study revealed a previously unknown function of ANKRD1 in renal IRI. By driving ACSL3 ubiquitination and degradation, ANKRD1 aggravates ferroptosis and ultimately exacerbates IRI‐AKI, underlining ANKRD1's potential as a therapeutic target for kidney IRI.Key Points/Highlights Ankyrin repeat domain 1 (ANKRD1) is rapidly activated in renal ischaemia‒reperfusion injury (IRI) models in vivo and in vitro. ANKRD1 knockdown mitigates kidney damage and preserves renal function. Ferroptosis contributes to the deteriorating function of ANKRD1 in renal IRI. ANKRD1 promotes acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3) degradation via the ubiquitin‒proteasome pathway. The E3 ligase tripartite motif containing 25 (TRIM25) is responsible for ANKRD1‐mediated ubiquitination of ACSL3.

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Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases

Cited by 9 publications

References 165 publications

Role of ferroptosis in chronic kidney disease

Role of ferroptosis in chronic kidney disease

Ferroptosis: a potential bridge linking gut microbiota and chronic kidney disease

ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25‐mediated ubiquitination of ACSL3

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