Oxygen modulates iron homeostasis by switching iron sensing of NCOA4

Kuno, Sota; Iwaï, Kazuhiro

doi:10.1016/j.jbc.2023.104701

Cited by 16 publications

(8 citation statements)

References 47 publications

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“…However, whether hypoxia attenuates transcription of NCOA4 is still controversial and requires further analysis. In addition to the report of Fuhrman et al 57 , NCOA4 degradation by HERC 2 has been shown to be promoted by Fe‐S insertion into NCOA4 upon hypoxic condition 51 . On the other hand, NCOA4 has been reported to be upregulated upon hypoxia through the binding of HIF1α/β to HRE in 5′ UTR of NCOA4 58 .…”

Section: Regulation Of Ftmt Expressionmentioning

confidence: 79%

“…Goodwin et al identified an alternative lysosomal transport pathway for ferritin that requires FIP200, ATG9, vacuolar protein sorting 34 (VPS34) and TAX1BP1 but lacks LC3 lipidation 49 . As described above, NCOA4 forms insoluble condensates with or without ferritin under iron repletion 50,51 . This sequesters NCOA4 away from ferritin and allows ferritin accumulation in the early phase of iron repletion.…”

Section: Ferritin Fate Entrusted To Nuclear Receptor Coactivator 4 (N...mentioning

confidence: 98%

“…49 As described above, NCOA4 forms insoluble condensates with or without ferritin under iron repletion. 50,51 This sequesters NCOA4 away from ferritin and allows ferritin accumulation in the early phase of iron repletion. Under prolonged iron repletion, NCOA4 condensates can deliver ferritin to lysosomes via a TAXBP1dependent noncanonical autophagy pathway.…”

Section: Degradation Of Ferritin Via the Alternative Lysosomal Transp...mentioning

confidence: 99%

“…In addition to the report of Fuhrman et al 57 , NCOA4 degradation by HERC 2 has been shown to be promoted by Fe-S insertion into NCOA4 upon hypoxic condition. 51 On the other hand, NCOA4 has been reported to be upregulated upon hypoxia through the binding of HIF1α/β to HRE in 5′ UTR of NCOA4. 58 FTH is degraded by NCOA4 through autophagy (ferritinophagy).…”

Section: Hypoxia and Ftmt Expressionmentioning

confidence: 99%

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Newly uncovered biochemical and functional aspects of ferritin

et al. 2023

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Iron homeostasis is strictly regulated at both the systemic and cellular levels by complex mechanisms because of its indispensability and toxicity. Among the various iron‐regulatory proteins, ferritin is the earliest discovered regulator of iron metabolism and is a molecule that safely retains excess intracellular iron in the cores of its shells. Two types of ferritin, cytosolic ferritin and mitochondrial ferritin (FTMT), have been identified in a range of organisms from plants to humans. FTMT was identified approximately 60 years after the discovery of cytosolic ferritin. Cytosolic ferritin expression is regulated in an iron‐responsive manner. Recently, the molecular mechanisms of iron‐dependent degradation of cytosolic ferritin or its secretion into serum have been clarified. FTMT, which shares a high degree of sequence homology with cytosolic ferritin, has distinct functions and is regulated in different ways from cytosolic ferritin. Although knowledge of the physiological role of FTMT is still incomplete, recent studies have shed light on the function and regulation of FTMT. The accumulating biological evidence of both ferritins has made it possible to deepen our knowledge about iron metabolism and its significance in diseases. In this review, we discuss the biological properties of both ferritins, focusing on their newly uncovered behaviors.

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Section: Regulation Of Ftmt Expressionmentioning

confidence: 79%

Section: Ferritin Fate Entrusted To Nuclear Receptor Coactivator 4 (N...mentioning

confidence: 98%

Section: Degradation Of Ferritin Via the Alternative Lysosomal Transp...mentioning

confidence: 99%

Section: Hypoxia and Ftmt Expressionmentioning

confidence: 99%

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Newly uncovered biochemical and functional aspects of ferritin

et al. 2023

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“…This binding allows ferritin to be encapsulated into autophagosomes, which are then transported to lysosomes, also FTH1 (heavy chain ferritin), as one of the main components of the ferritin complex, may play a regulatory role in this process (Tian et al, 2020). Taken together, NCOA4 contributes to ferritinophagy through the processes of recognition, encapsulation, fusion, and degradation (Kuno & Iwai, 2023). FTH1, on the other hand, plays a role in the regulation of ferritinophagy, helping cells to release or store iron ions as needed.…”

Section: Ferritinophagy and Hccmentioning

confidence: 99%

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

Chen,

Tan,

Zhang

et al. 2024

Phytotherapy Research

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Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer‐related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy‐related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy‐modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β‐catenin, Beclin‐1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double‐edged sword in HCC management.

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Unveiling the stochastic nature of human heteropolymer ferritin self‐assembly mechanism

Bou‐Abdallah,

Fish,

Terashi

et al. 2024

Protein Science

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Despite ferritin's critical role in regulating cellular and systemic iron levels, our understanding of the structure and assembly mechanism of isoferritins, discovered over eight decades ago, remains limited. Unveiling how the composition and molecular architecture of hetero‐oligomeric ferritins confer distinct functionality to isoferritins is essential to understanding how the structural intricacies of H and L subunits influence their interactions with cellular machinery. In this study, ferritin heteropolymers with specific H to L subunit ratios were synthesized using a uniquely engineered plasmid design, followed by high‐resolution cryo‐electron microscopy analysis and deep learning‐based amino acid modeling. Our structural examination revealed unique architectural features during the self‐assembly mechanism of heteropolymer ferritins and demonstrated a significant preference for H‐L heterodimer formation over H‐H or L‐L homodimers. Unexpectedly, while dimers seem essential building blocks in the protein self‐assembly process, the overall mechanism of ferritin self‐assembly is observed to proceed randomly through diverse pathways. The physiological significance of these findings is discussed including how ferritin microheterogeneity could represent a tissue‐specific adaptation process that imparts distinctive tissue‐specific functions to isoferritins.

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Oxygen modulates iron homeostasis by switching iron sensing of NCOA4

Cited by 16 publications

References 47 publications

Newly uncovered biochemical and functional aspects of ferritin

Newly uncovered biochemical and functional aspects of ferritin

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

Unveiling the stochastic nature of human heteropolymer ferritin self‐assembly mechanism

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