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    Home > Medical News > Latest Medical News > Li Lanjuan's team: The mitochondrial mechanism of necrotizing apoptosis in liver disease

    Li Lanjuan's team: The mitochondrial mechanism of necrotizing apoptosis in liver disease

    • Last Update: 2021-06-10
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    New progress in liver disease research by the team of academician Li Lanjuan: the mitochondrial mechanism of necrotizing apoptosis in liver disease | MDPI IJMS
    New Progress in Liver Disease Research of Academician Li Lanjuan's Team: Mitochondrial Mechanism of Necroptosis in Liver Disease | MDPI IJMS New Progress in Liver Disease Research of Academician Li Lanjuan's Team: Mitochondrial Mechanism of Necrotic Apoptosis in Liver Disease | MDPI IJMS

    Paper Title: Mitochondrial Mechanisms of Necroptosis in Liver Diseases (Mitochondrial Mechanisms of Necroptosis in Liver Diseases)

    Journal: IJMS

    Authors: Chen Xue, Xinyu Gu, Ganglei Li, Zhengyi Bao and Lanjuan Li

    Posting time: 23 December 2020

    DOI: 10.
    3390/ijms22010066

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    Journal link:

    https:// href="https://" target="_blank">https:// style="color:#0000ff;"> https:// style="text-indent:2em"> Liver diseases, including hepatitis B, hepatitis C, non-alcoholic and alcoholic steatohepatitis and related liver diseases such as liver fibrosis, cirrhosis, liver failure and hepatocellular carcinoma, are one of the main causes of disease and death in the world .
    Although people have conducted extensive research on the pathogenesis of various liver diseases, there is still no effective treatment for end-stage liver diseases.
    Therefore, it is essential to better understand the molecular mechanisms of liver disease and develop potential therapeutic targets.

    Image source: Pixabay

    Image source: Pixabay

    Mitochondria regulate cell necroptosis

    Mitochondria regulate cell necroptosis

    Necroptosis is a common and controllable form of programmed cell necrosis in the liver.
    Its activation does not depend on caspase and has the common characteristics of necrosis and apoptosis.
    A review published by the team of
    Academician Li Lanjuan from Zhejiang University School of Medicine in IJMS reviewed the various molecular mechanisms of mitochondria-mediated cell necrosis and discussed its role in a variety of liver diseases and potential clinical studies.
    The study of pathophysiology of liver disease and its treatment methods provide enlightenment.

    academician

    Although the specific mechanism of the necrosome complex inducing cell necroptosis is still unclear, some studies have shown that the generation of ROS is closely related to cell necroptosis.
    For example, ROS can promote RIPK1 autophosphorylation in some cells; In addition, as shown in Figure 1, the dual function of mitochondrial PGAM5 plays an important role in cell necrosis; as shown in Figure 2, phosphorylated RIPK3 can directly increase the activity of some metabolic enzymes in the tumor necrosis factor induction pathway , Such as: glutamate ammonia ligase (GLUL) and glutamate dehydrogenase 1 (GLUD1) induce cell necrosis; at the same time, the author also summarized the mitochondrial permeability transition pore and cyclophilin D, B cells Lymphoma 2 (BCL-2) protein family and other mitochondrial mechanisms regulate cell necroptosis; the above multiple mechanisms indicate that mitochondria and their metabolism play an important role in the regulation of cell necroptosis.

    Figure 1.
    The dual function of PGAM5 in cell necroptosis

    Figure 1.
    The dual function of PGAM5 in cell necroptosis

    Figure 2.
    The role of mitochondrial metabolic enzymes in cell necroptosis

    Figure 2.
    The role of mitochondrial metabolic enzymes in cell necroptosis

    Mitochondrial mechanism of necrotizing apoptosis in liver disease

    Mitochondrial mechanism of necrotizing apoptosis in liver disease

    Mitochondrial dysfunction is related to acute liver injury.
    The author first discussed the mitochondrial mechanism of necroptosis in acute liver injury.
    For example, when Listeria monocytogenes infection causes acute liver injury in mice, RIPK1/RIPK3/MLKL signal The pathway is activated, which subsequently leads to necroptosis and liver damage; knocking out the RIPK1 gene can alleviate mitochondrial dysfunction and necroptosis in the liver tissue of infected mice.

    Subsequently, the author discussed the mechanism of mitochondrial necroptosis in chronic liver disease.
    Although a large number of studies have confirmed that there is a clear connection between apoptosis and chronic liver disease, the occurrence of necroptosis and its effect on chronic liver disease are controversial.
    This contradiction is that theoretically the occurrence of necroptosis depends on RIPK3, but the expression of RIPK3 has not been detected in primary mouse liver cells.
    Nevertheless, more and more studies at the liver level reflect that mitochondrial dysfunction may lead to chronic liver disease.
    In addition, many studies have shown that necroptosis occurs in liver cancer cells through mitochondrial-related signaling pathways.
    N-terminal kinase (JNK), BAX, BAK and other proteins play an important role in the regulation of mitochondria in the process of necrotic apoptosis in liver cancer cells.

    Analysis conclusion

    Analysis conclusion

    In various liver diseases, mitochondria are multi-faceted regulators of the necrotizing apoptotic pathway, which play multiple functions such as promoting inflammation, enhancing immune response and regulating disease progression.
    Necroptosis leads to mitochondrial dysfunction through PIPK1/PIPK3/MLKL pathway.
    With the advancement of gene editing technology, it has become possible to correct important mutated genes in the mitochondrial-mediated pathway, thereby improving the progress of certain liver diseases.
    However, before identifying safe and effective inhibitors or drugs that improve mitochondrial function, scientists still have a lot of work to do.

    Research Outlook

    Research Outlook

    Mitochondria play an important regulatory role in cell necrotic apoptosis, which implies that the prevention and treatment of liver disease by targeting to inhibit the apoptosis/necrosis pathway induced by mitochondria has great prospects.
    Just as the academics have discovered, in non-alcoholic fatty liver, the necroptotic pathway is activated, and inhibition of RIPK1 can improve the characteristics of non-alcoholic steatohepatitis in mice fed with high-fat diet.
    Although some progress has been made in the mechanism of mitochondrial necrosis in a variety of liver diseases, the current studies are mostly done in animal models of liver diseases, which cannot fully reflect all the characteristics of human liver diseases.
    Many methods have been reported to target mitochondrial disorders to treat liver disease, but there are still many non-specific reactions.
    Therefore, it is necessary to develop and test small molecular targets for specific steps in the mitochondrial-mediated cell death signaling pathway.

    Journal Introduction

    Journal Introduction

    International Journal of Molecular Sciences (IJMS) (ISSN 1422-0067; IF 4.
    556) is an international peer-reviewed open access journal, covering topics such as biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and chemical molecular research, etc.
    aspect.
    IJMS adopts single-blind peer review, the first review cycle is about 10 days, and the article only needs 2 days from receipt to publication.

    International Journal of Molecular Sciences International Journal of Molecular Sciences International Journal of Molecular Sciences IJMS IJMS IJMS

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