Mfn2-mediated mitochondrial fusion promotes autophagy and suppresses ovarian cancer progression by reducing ROS through AMPK/mTOR/ERK signaling

Ashraf, Rahail; Kumar, Sanjay

doi:10.1007/s00018-022-04595-6

Cited by 40 publications

(26 citation statements)

References 66 publications

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“…Moreover, following TRIM22 knockdown, protein phosphorylation levels of AMPK and ERK decreased, whereas that of mTOR increased. Previous studies showed that AMPK/ERK/mTOR signaling pathway plays a key role in the regulation of autophagy, and its main mechanism is that AMPK regulates autophagy by inhibiting downstream mTOR, which may be an activation mode of AMPK/ERK/mTOR signal in the regulation of autophagy [ 41 – 43 ]. These results suggest that TRIM22 activates autophagy through the AMPK/ERK/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs

Gou

et al. 2022

Virol J

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Background Dengue virus type 2 (DENV-2) was used to infect primary human umbilical vein endothelial cells (HUVECs) to examine autophagy induced by activation of the adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway following tripartite motif-containing 22 (TRIM22)-mediated DENV-2 infection to further reveal the underlying pathogenic mechanism of DENV-2 infection. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen putative interference targets of TRIM22 and determine the knockdown efficiency. The effect of TRIM22 knockdown on HUVEC proliferation was determined using the CCK8 assay. Following TRIM22 knockdown, transmission electron microscopy (TEM) was used to determine the ultrastructure of HUVEC autophagosomes and expression of HUVEC autophagy and AMPK pathway-related genes were measured by qRT-PCR. Moreover, HUVEC autophagy and AMPK pathway-related protein expression levels were determined by western blot analysis. Cell cycle and apoptosis were assessed by flow cytometry (FCM) and the autophagosome structure of the HUVECs was observed by TEM. Results Western blot results indicated that TRIM22 protein expression levels increased significantly 36 h after DENV-2 infection, which was consistent with the proteomics prediction. The CCK8 assay revealed that HUVEC proliferation was reduced following TRIM22 knockdown (P < 0.001). The TEM results indicated that HUVEC autolysosomes increased and autophagy was inhibited after TRIM22 knockdown. The qRT-PCR results revealed that after TRIM22 knockdown, the expression levels of antithymocyte globulin 7 (ATG7), antithymocyte globulin 5 (ATG5), Beclin1, ERK, and mTOR genes decreased (P < 0.01); however, the expression of AMPK genes (P < 0.05) and P62 genes (P < 0.001) increased. FCM revealed that following TRIM22 knockdown, the percentage of HUVECs in the G2 phase increased (P < 0.001) along with cell apoptosis. The effect of TRIM22 overexpression on HUVEC autophagy induced by DENV-2 infection and AMPK pathways decreased after adding an autophagy inhibitor. Conclusions In HUVECs, TRIM22 protein positively regulates autophagy and may affect autophagy through the AMPK/ERK/mTOR signaling pathway. Autophagy is induced by activation of the AMPK/ERK/mTOR signaling pathway following TRIM22-mediated DENV-2 infection of HUVECs.

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Section: Discussionmentioning

confidence: 99%

Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs

Gou

et al. 2022

Virol J

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“…MAMs are initiation sites of autophagosome formation [ 82 , 83 ]. In addition, knockdown of MFN2 evokes impaired autophagy [ 84 , 85 ]. By contrast, overexpression of MFN2 leads to the induction of autophagy [ 85 ].…”

Section: Bas As Regulatory Modulatorsmentioning

confidence: 99%

“…In addition, knockdown of MFN2 evokes impaired autophagy [ 84 , 85 ]. By contrast, overexpression of MFN2 leads to the induction of autophagy [ 85 ]. In addition, it is critical to maintain a balance between mitochondrial fusion and fission to support both mitochondrial and cellular function, and mitochondrial structural changes are associated with neurodegenerative diseases.…”

Section: Bas As Regulatory Modulatorsmentioning

confidence: 99%

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

Kiriyama

Nochi

2023

Genes

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Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety of ways by different types of bacteria present in the gut microbiota, changes in the gut microbiota can affect the metabolism of BAs in the host. Although most BAs absorbed from the gut are transferred to the liver, some are transferred to the systemic circulation. Furthermore, BAs have also been detected in the brain and are thought to migrate into the brain through the systemic circulation. Although BAs are known to affect a variety of physiological functions by acting as ligands for various nuclear and cell-surface receptors, BAs have also been found to act on mitochondria and autophagy in the cell. This review focuses on the BAs modified by the gut microbiota and their roles in intracellular organelles and neurodegenerative diseases.

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“…The supplementation of OC cells with hydrogen sulfide or gluthatione (the products of CBS activity) restored the expression of MFN2 improving mitochondrial morphology and sustaining tumours cell proliferation [ 115 ]. On the other hand, another study reported that OC patients with higher MFN2 expression had better survival than those with lower MFN2 levels and pharmacological or genetic activation of MFN2 leading to mitochondrial fusion and decreased ROS generation, resulting in reduced cell proliferation [ 116 ].…”

Section: Mitochondrial Dynamics In Ovarian Cancermentioning

confidence: 99%

Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics

Rasmo

Cormio

et al. 2023

IJMS

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Ovarian cancer (OC) represents the main cause of death from gynecological malignancies in western countries. Altered cellular and mitochondrial metabolism are considered hallmarks in cancer disease. Several mitochondrial aspects have been found altered in OC, such as the oxidative phosphorylation system, oxidative stress and mitochondrial dynamics. Mitochondrial dynamics includes cristae remodeling, fusion, and fission processes forming a dynamic mitochondrial network. Alteration of mitochondrial dynamics is associated with metabolic change in tumour development and, in particular, the mitochondrial shaping proteins appear also to be responsible for the chemosensitivity and/or chemoresistance in OC. In this review a focus on the mitochondrial dynamics in OC cells is presented.

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Mfn2-mediated mitochondrial fusion promotes autophagy and suppresses ovarian cancer progression by reducing ROS through AMPK/mTOR/ERK signaling

Cited by 40 publications

References 66 publications

Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs

Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics

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