China
Africa
Explore chapters and articles related to this topic
The Contribution of Iron and Transition Metal Micronutrients to Diabetes and Metabolic Disease
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Lipika Salaye, Zhenzhong Bai, Donald A. McClain
A relatively recent discovery in this picture is the recycling of iron from its ferritin-sequestered state. This is accomplished by a specialized form of autophagy, ferritinophagy. Autophagosomes are targeted to ferritin by the protein NCOA4, which is stabilized under conditions of low cytosolic iron [14]. The process thus results in ferritin degradation and release of iron stores when tissue iron levels fall. All of the processes involved in iron trafficking—chaperoning, sequestration by ferritin, ferritinophagy, and incorporation into prosthetic groups—mean that total intracellular iron levels may have very different consequences to cell function, depending on whether the iron is free, safely sequestered in ferritin, or incorporated into heme or iron-sulfur clusters. Thus, understanding the functional intracellular iron status requires knowledge of its flux and compartmentalization [6,15], which can be at least partially inferred from levels of TfR mRNA, NCOA4, ferritin, heme-bound iron, and so on.
Nuclear Receptor Coactivators: Mechanism and Therapeutic Targeting in Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Andrew Cannon, Christopher Thompson, Rakesh Bhatia, Sushil Kumar
In hormone insensitive cancers, the actions of NCOA4 in cancer pathobiology do not seem to broadly involve the wild-type transcript. Many studies have indicated, however, that physical modification of chromosome 10 subjugates the NCOA4 and RET genes to a breakage-repair event resulting in a fusion product. Ghandhi et al. conducted chromosomal rearrangement analysis and observed that NCOA4 and RET genes are separated by nearly 8 Mb, but interphase coiling brings them within 0.87 µM of each other, closer than any other RET neighboring genes [96]. Despite the proximity of NCOA4 and RET, this fusion event is rare and has been detected in only a handful of patients with different malignancies such as thyroid cancers [97–101], NSCLC [98, 99, 102, 103], CRC [98, 104-106], and salivary carcinoma [107]. NCOA4-RET fusion seems to be more prominent in papillary thyroid carcinoma (PTC) with around 10% of patients harboring a RET fusion and about 90% of those fusions occur with NCOA4 [96–100]. These studies also demonstrate that the pathological consequences of NCOA4-RET fusion are likely attributed to the constitutive activation of the RET tyrosine kinase domain and subsequent NIAPK signaling. Interestingly, patients having this particular mutation were found to have no other mutations strongly implicated in their respective cancers. The conclusions made by each of these studies are that the minor groups of patients with tumors harboring NCOA4-RET fusions are likely to benefit from treatment with multi-tyrosine kinase inhibitors instead of other first-line therapies and personalized approaches to cancer intervention may likely require identifying this mutation at diagnosis.
Schisandrin B promotes senescence of activated hepatic stellate cell via NCOA4-mediated ferritinophagy
Published in Pharmaceutical Biology, 2023
Mingyue Ma, Na Wei, Jieren Yang, Tingting Ding, Anping Song, Lerong Chen, Shuguo Zheng, Huanhuan Jin
Ferritinophagy can be categorized into two parts: the formation of autophagosomes and the targeted recognition of ferritin (Xiu et al. 2022). NCOA4 is a selective cargo receptor that mediates the autophagic degradation of iron proteins in the cytoplasmic iron storage complex (Mancias et al. 2015; Santana-Codina and Mancias 2018; Kong et al. 2019; Li et al. 2020). In the current study, Sch B elevated the expression of LC3B and NCOA4 and promoted protein-protein interaction between NCOA4 and FTH1. These results indicated that the promotion of iron overload by Sch B might be due to its induction of ferritinophagy. Subsequently, si-NCOA4 was used to investigate the role of ferritinophagy on Sch B’s regulation of iron overload and cellular senescence. The results indicated that si-NCOA4 could reverse Sch B’s induction of iron overload, ROS production and cellular senescence in LX2 cells. These data provided further evidence for the notion that Sch B’s induction of cellular senescence might be derived from its activation of ferrtinophagy in HSCs.
Puerarin Induces Ferroptosis in Colorectal Cancer Cells via Triggering NCOA4 Upregulation
Published in Nutrition and Cancer, 2023
Guo Lian, Xi-xi Huang, Yan Zeng
We also wondered whether puerarin affects autophagy, given that ferroptosis depends on this recycling process (11–13). Autophagy leads to the release of iron from ferritin through a process called ferritinophagy (14), which increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation (15). Nuclear receptor coactivator 4 (NCOA4) binds to ferritin and leads to its sequestration in lysosomes, where the iron is released (16). NCOA4, a selective cargo receptor, which modulates the the autophagic degradation of ferritin, the cytosolic iron storage complex, in a process known as ferritinophagy (16). Moreover, NCOA4-facilitated ferritinophagy may be modulated by autophagy-related (ATG) genes (17). ATG genes play an important role in the mediation of autophagy. Among them, ATG5 is critical for the formation of the autophagosome (11). Moreover, some researchers have showed a preference for fusion partners in different tumor types, with KIF5B being the common type in lung cancer, CCDC6 in thyroid cancer, and NCOA4 in colorectal cancer (18). We speculated that NCOA4 may be involved in the pathological mechanism of colorectal cancer. Therefore, using the colorectal cell cancer line HT-29, we explored here whether and how puerarin induces tumor cell death by influencing ferroptosis and ferritinophagy.
Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
Published in Renal Failure, 2021
Yun Tang, Haojun Luo, Qiong Xiao, Li Li, Xiang Zhong, Jiong Zhang, Fang Wang, Guisen Li, Li Wang, Yi Li
The results of western blot with murine kidney tissues suggested that LPS injection could increase the expression of NOCA4 in mice kidney, whereas ISL could inhibit the expression of NCOA4 in mice kidney following LPS injection (Figure 7(A)). Although LPS could significantly increase the level of NOCA4 in HK2 cells, both 50 µM and 100 µM ISL could reduce the expression of NCOA4 in HK2 cells following LPS induction (Figure 7(B)). Immunohistochemical staining with NCOA4 showed LPS significant increase in the expression of NCOA4 in murine renal tubular. However, ISL treatment could decrease the expression of NCOA4 in murine renal tubular upon LPS injection (Figure 7(C)).