Mitochondria, mitophagy, and the role of deubiquitinases as novel therapeutic targets in liver pathology

Aryapour, Elham; Kietzmann, Thomas

doi:10.1002/jcb.30312

Cited by 7 publications

(7 citation statements)

References 70 publications

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“…Some physiological errors in mitochondria, possibly due to oxidative stress, may initiate the mitophagy via the disruption of the mitochondrial membrane by ROS. ( Figure 1 ) A reduction in mitochondrial quality has been suggested to play a major role in the development and/or progression of MAFLD [ 36 , 37 ]. Additionally, the imbalance of the mitophagy in hepatocytes could promote the development of MAFLD [ 38 ].…”

Section: Dysfunction Of Mitochondria Involved In the Pathogenesis Of ...mentioning

confidence: 99%

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

Tsuji

Yoshikawa

Ikeda

et al. 2023

IJMS

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Mitophagy/autophagy plays a protective role in various forms of liver damage, by renovating cellular metabolism linking to sustain liver homeostasis. A characterized pathway for mitophagy is the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkin-dependent signaling pathway. In particular, PINK1-mediated mitophagy could play an indispensable role in improving the metabolic dysfunction-associated fatty liver disease (MAFLD) which could precede to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. In addition, the PI3K/AKT/mTOR pathway might regulate the various characteristics of cellular homeostasis including energy metabolism, cell proliferation, and/or cell protection. Therefore, targeting mitophagy with the alteration of PI3K/AKT/mTOR or PINK1/Parkin-dependent signaling to eliminate impaired mitochondria might be an attractive strategy for the treatment of MAFLD. In particular, the efficacy of prebiotics for the treatment of MAFLD has been suggested to be useful via the modulation of the PI3K/AKT/mTOR/AMPK pathway. Additionally, several edible phytochemicals could activate mitophagy for the improvement of mitochondrial damages, which could also be a promising option to treat MAFLD with providing liver protection. Here, the potential therapeutics with several phytochemicals has been discussed for the treatment of MAFLD. Tactics with a viewpoint of prospective probiotics might contribute to the development of therapeutic interventions.

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Section: Dysfunction Of Mitochondria Involved In the Pathogenesis Of ...mentioning

confidence: 99%

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

Tsuji

Yoshikawa

Ikeda

et al. 2023

IJMS

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“…SFAs, such as PAs, are known to impair mitochondrial energetics, resulting in reduced ATP production followed by accelerated mitochondrial reactive oxygen species (ROS) production [ 66 ]. In this context, mitochondrial autophagy, known as “mitophagy,” is a process of mitochondrial pruning, which prevents the induction of lipoapoptosis in response to oxidative stress [ 67 , 68 ]. Defective mitophagy has been demonstrated in both human NASH and high fat diet (HFD)-induced in vivo mouse models, as well as in cultured hepatocytes treated with SFAs, associating with oxidative stress and lipoapoptosis [ 68 ].…”

Section: Autophagy Induction Mitigates Hepatic Lipotoxicitymentioning

confidence: 99%

Autophagy: A Cellular Guardian against Hepatic Lipotoxicity

Sinha

2023

Genes

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Lipotoxicity is a phenomenon of lipid-induced cellular injury in nonadipose tissue. Excess of free saturated fatty acids (SFAs) contributes to hepatic injury in nonalcoholic fatty liver disease (NAFLD), which has been growing at an unprecedented rate in recent years. SFAs and their derivatives such as ceramides and membrane phospholipids have been shown to induce intrahepatic oxidative damage and ER stress. Autophagy represents a cellular housekeeping mechanism to counter the perturbation in organelle function and activation of stress signals within the cell. Several aspects of autophagy, including lipid droplet assembly, lipophagy, mitophagy, redox signaling and ER-phagy, play a critical role in mounting a strong defense against lipotoxic lipid species within the hepatic cells. This review provides a succinct overview of our current understanding of autophagy–lipotoxicity interaction and its pharmacological and nonpharmacological modulation in treating NAFLD.

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“…HCC cells gain energy to migrate outward through autophagy and enhance the degree of cell adhesion, thus contributing to metastasis and RHCC. 39 Autophagy is also an important factor in the induction of EMT, which is activated by the HIF-1α/BNIP3 pathway through autophagy in HCC cells. This process produces extracellular matrix, degrades enzymes, and increases the resistance of HCC cells to apoptosis.…”

Section: Role Of the Hif-1α/bnip3 Signaling Pathway In Rhccmentioning

confidence: 99%

Role of the HIF-1α/BNIP3 Signaling Pathway in Recurrent Hepatocellular Carcinoma and the Mechanism of Traditional Chinese Medicine

Liu¹,

Kang²,

Song³

et al. 2023

JHC

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Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.

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Mitochondria, mitophagy, and the role of deubiquitinases as novel therapeutic targets in liver pathology

Cited by 7 publications

References 70 publications

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

Autophagy: A Cellular Guardian against Hepatic Lipotoxicity

Role of the HIF-1α/BNIP3 Signaling Pathway in Recurrent Hepatocellular Carcinoma and the Mechanism of Traditional Chinese Medicine

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