PGAM5 regulates DRP1-mediated mitochondrial fission/mitophagy flux in lipid overload-induced renal tubular epithelial cell necroptosis

Sang, Dan; Duan, Xiaoyang; Yu, Xiangbin; Zang, Jiabin; Liu, Lan; Wu, Guifu

doi:10.1016/j.toxlet.2022.10.003

Cited by 11 publications

(3 citation statements)

References 39 publications

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“…Studies have shown that excessive mitochondrial fission is associated with reactive oxygen species (ROS) leakage(39), which is the major signal of triggering necroptosis. After fission, mitochondria cannot to acidic lysosomes for circulating, and continuous overproduction of ROS in mitochondrial (mtROS) eventually leads to necroptosis(22). Thus, we speculate that excessive mitochondrial fission in URSA may increase necroptosis activated by mtROS, thereby disrupting decidualization.…”

Section: Discussionmentioning

confidence: 99%

“…This indicated that mitochondrial fission was significantly active in URSA. Moreover, given that mitochondrial fission is increased in URSA, and that mitochondrial fission is closely related to necroptosis (21)(22)(23), we further explored the effect of mitochondrial fission on necroptosis and decidualization in vitro. First, TA9 was applied to successfully induce mitochondrial fission, characterized by the increased expression of (western blot: Drp1 P<0.05; Fis1 P<0.01. immunofluorescence: Drp1 and Fis1 P<0.05) (Figure 4A-D).…”

Section: Mitochondrial Fission Was Significantly Active In Ursamentioning

confidence: 99%

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Baicalin Ameliorates Defective Decidualization in URSA by Regulating Mitochondrial Fission Induced Necroptosis

Zhao

Yang

et al. 2023

Preprint

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Defective decidualization is a significant pathological feature of URSA. And the potential relationship between mitochondrial fission, necroptosis and defective decidualization remains unknown. Baicalin plays an important role in regulating mitochondrial fission and programmed cell death. However, whether baicalin has a protective effect on defective decidualization in URSA has not been reported thus far. This study aims to explore the mechanisms of mitochondrial fission induced necroptosis in defective decidualization in URSA and the regulation of baicalin. First, decidual tissues were collected from URSA and health controls. And then, T-hESC was treated with lipopolysaccharide (LPS), Tyrphostin A9 (TA9), TA9+necrostatin-1(Nec-1) and TA9+baicalin during in vitro decidualization. Besides, URSA mice were established and randomly administrated with low, medium, and high doses of baicalin as well as saline. Results showed that decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein-1 (IGFBP1) in patients with URSA were significantly decreased (P<0.05). The incidence of cell necroptosis was increased, manifested with increased Annexin V and PI positive cells, high level of pRIP3 T231(P<0.01) and pMLKL S358 (P<0.05). Moreover, mitochondrial fission was also hyperactive, featured by elevated level of Fis1 (P<0.01) and Drp1 (P<0.05). In vitro experiments, LPS was induced to trigger necroptosis of T-hESC during induced decidualization, and IGFBP1 and PRL were subsequently decreased (P<0.05). Besides, mitochondrial fission inducer TA9 promoted the level of necroptosis (P<0.05) and induced defective decidualization, which could be rescued by necroptosis inhibitor Nec-1 (P<0.05). In addition, baicalin could reduce mitochondrial fission (P<0.05), necroptosis (P<0.05) and ameliorate defective decidualization in vivo and in vitro (P<0.05). In conclusion, hyperactive mitochondrial fission could promote necroptosis, thus inducing defective decidualization. And baicalin could ameliorates defective decidualization in URSA by regulating mitochondrial fission induced necroptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Mitochondrial Fission Was Significantly Active In Ursamentioning

confidence: 99%

Baicalin Ameliorates Defective Decidualization in URSA by Regulating Mitochondrial Fission Induced Necroptosis

Zhao

Yang

et al. 2023

Preprint

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“…PGAM5s recruits mitochondrial division factor kinetic-related protein 1 (Drp1), which is activated upon dephosphorylation. Activated Drp1 triggers mitochondrial cleavage and ROS production, eventually inducing necroptosis [ 52 ]. In addition to the RIPK1–RIPK3–MLKL signaling cascade, activation of CaMKII is another mechanism of necroptosis induction.…”

Section: Role Of Ripk3 In Necroptosismentioning

confidence: 99%

RIPK3 signaling and its role in regulated cell death and diseases

Zhou,

Xiang,

Liu

et al. 2024

Cell Death Discov.

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Receptor-interacting protein kinase 3 (RIPK3), a member of the receptor-interacting protein kinase (RIPK) family with serine/threonine protein kinase activity, interacts with RIPK1 to generate necrosomes, which trigger caspase-independent programmed necrosis. As a vital component of necrosomes, RIPK3 plays an indispensable role in necroptosis, which is crucial for human life and health. In addition, RIPK3 participates in the pathological process of several infections, aseptic inflammatory diseases, and tumors (including tumor-promoting and -suppressive activities) by regulating autophagy, cell proliferation, and the metabolism and production of chemokines/cytokines. This review summarizes the recent research progress of the regulators of the RIPK3 signaling pathway and discusses the potential role of RIPK3/necroptosis in the aetiopathogenesis of various diseases. An in-depth understanding of the mechanisms and functions of RIPK3 may facilitate the development of novel therapeutic strategies.

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Baicalin ameliorates deficient decidualization in URSA by regulating mitochondrial fission induced necroptosis

Zhao,

Yang

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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PGAM5 regulates DRP1-mediated mitochondrial fission/mitophagy flux in lipid overload-induced renal tubular epithelial cell necroptosis

Cited by 11 publications

References 39 publications

Baicalin Ameliorates Defective Decidualization in URSA by Regulating Mitochondrial Fission Induced Necroptosis

Baicalin Ameliorates Defective Decidualization in URSA by Regulating Mitochondrial Fission Induced Necroptosis

RIPK3 signaling and its role in regulated cell death and diseases

Baicalin ameliorates deficient decidualization in URSA by regulating mitochondrial fission induced necroptosis

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