Mitophagy: A crucial modulator in the pathogenesis of chronic diseases

Yang, Xiaobin; Pan, Weinan; Xu, Gaolian; Chen, Linxi

doi:10.1016/j.cca.2019.11.008

Cited by 34 publications

(26 citation statements)

References 102 publications

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“…Mitophagy is a type of selective autophagy, playing an essential role in the maintenance of mitochondrial homeostasis [25]. Mitochondrial perturbation, reactive oxygen species (ROS), and oxidative stress can trigger mitophagy to degrade dysfunctional mitochondria as a mitochondrial quality control mechanism [25].…”

Section: Mitophagymentioning

confidence: 99%

Crosstalks between inflammasome and autophagy in cancer

et al. 2020

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Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anticancer strategies, although it remains underexplored in terms of their crosstalks.

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Section: Mitophagymentioning

confidence: 99%

Crosstalks between inflammasome and autophagy in cancer

et al. 2020

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“…In response to various stimuli, mitochondria undergo self-depolarization and the damaged organelles are identi ed by autophagosomes which then fuse with lysosomes to complete the degradation process [3,4]. Defective or excessive mitophagy is a pathological factor in chronic diseases like Parkinson's disease (PD), diabetes, Myocardial ischemia reperfusion (MIR) injury, ankylosing spondylitis (AS) and cancer [5]. Several mitophagic pathways have been identi ed that counteract therapy-induced mitochondrial damage [5,6] .…”

Section: Introductionmentioning

confidence: 99%

“…Defective or excessive mitophagy is a pathological factor in chronic diseases like Parkinson's disease (PD), diabetes, Myocardial ischemia reperfusion (MIR) injury, ankylosing spondylitis (AS) and cancer [5]. Several mitophagic pathways have been identi ed that counteract therapy-induced mitochondrial damage [5,6] . Guo et al reported that reversing mitophagy inhibition by the PIK3CA/AKT1/MTOR /RPS6KB1 pathway reduced the risk of colorectal cancer (CRC) development [7].…”

Section: Introductionmentioning

confidence: 99%

Mitophagy Promotes Sorafenib Resistance through Hypoxia-Inducible ATAD3A Dependent Axis

Wang

Liu

et al. 2020

Preprint

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Background: The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here, we identified hyperactivated mitophagy is essential for sorafenib resistance, and the mitophagy core regulator gene ATAD3A (ATPase family AAA domain containing 3A) was down regulated in hypoxia induced resistant HCC cells. Blocking mitophagy may restore the sorafenib sensitivity of these cells and provide a new treatment strategy for HCC patients. Methods: Hypoxia induced sorafenib resistant cancer cells were established by culturing under 1% O 2 with increasing drug treatment. RNA sequencing was conducted in transfecting LM3 cells with sh-ATAD3A lentivirus. Subsequent mechanistic studies were performed in HCC cell lines by manipulating ATAD3A expression isogenically where we evaluated drug sensitivity, molecular signaling events. In vivo study, we investigated the combined treatment effect of sorafenib and miR-210-5P antagomir. Results: We found a hyperactivated mitophagy regulating by ATAD3A-PINK/PARKIN axis in hypoxia induced sorafenib resistant HCC cells. Gain- and loss- of ATAD3A were related to hypoxia-induced mitophagy and sorafenib resistance. In addition, ATAD3A is a functional target of miR-210-5p and its oncogenic functions are likely mediated by increased miR-210-5P expression. miR-210-5P was upregulated under hypoxia and participated in regulating sorafenib resistance. In vivo xenograft assay showed that miR-210-5P antagomir combined with sorafenib abrogated the tumorigenic effect of ATAD3A down-regulation in mice. Conclusions: Loss of ATAD3A hyperactivates mitophagy which is a core event in hypoxia induced sorafenib resistance in HCC cells. Targeting miR-210-5P-ATAD3A axis is a novel therapeutic target for sorafenib-resistant HCC. Keywords: Mitophagy, ATAD3A, Hypoxia, Sorafenib resistance

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“…In response to various stimuli, mitochondria undergo self-depolarization and the damaged organelles are identi ed by autophagosomes which then fuse with lysosomes to complete the degradation process [3,4]. Defective or excessive mitophagy is a pathological factor in chronic diseases like Parkinson's disease (PD), diabetes, MIR injury, AS and cancer [5]. Several mitophagic pathways have been identi ed that counteract therapy-induced mitochondrial damage [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Defective or excessive mitophagy is a pathological factor in chronic diseases like Parkinson's disease (PD), diabetes, MIR injury, AS and cancer [5]. Several mitophagic pathways have been identi ed that counteract therapy-induced mitochondrial damage [5,6]. Guo et al reported that reversing mitophagy inhibition by the PIK3CA/AKT1/MTOR /RPS6KB1 pathway reduced the risk of CRC development [7].…”

Section: Introductionmentioning

confidence: 99%

Mitophagy Promotes Sorafenib Resistance Through a Hypoxia-Inducible ATAD3A Dependent Axis

Wang

Liu

et al. 2020

Preprint

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BACKGROUND: The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here we identified hyperactivated mitophagy is essential for sorafenib resistance, and the mitophagy core regulator gene ATAD3A (ATPase family AAA domain containing 3A) was down regulated in the resistant hepatoma cells. Blocking mitophagy may restore the sorafenib sensitivity of these cells and provide a new treatment strategy for HCC patients.METHODS: Hypoxia induced sorafenib resistant cells were established by culturing under 1% O2 with increasing drug treatment. RNA sequencing was conducted in transfecting LM3 cells with sh-ATAD3A lentivirus. Subsequent mechanistic studies were performed in HCC cell lines by manipulating ATAD3A expression isogenically where we evaluated drug sensitivity, molecular signaling events. In vivo study, we investigated the combined treatment effect of sorafenib and miR-210-5P antagomir. RESULTS: We found a hyperactivated mitophagy regulating by ATAD3A-PINK/PARKIN axis in hypoxia induced sorafenib resistant HCC cells. Gain- and loss- of ATAD3A were related to hypoxia-induced mitophagy and sorafenib resistance. In addition, ATAD3A is a functional target of miR-210-5p and its oncogenic functions are likely mediated by increased miR-210-5P expression. The classic hypoxia-induced miRNA was upregulated during hypoxia-induced mitophagy and sorafenib resistance. In vivo xenograft assay showed that miR-210-5P antagomir combined with sorafenib abrogated the tumorigenic effect of ATAD3A down-regulation in mice. CONCLUSION: Loss of ATAD3A hyperactivates mitophagy which is a core event in hypoxia induced sorafenib resistance in HCC cells. Targeting miR-210-5P-ATAD3A axis is a novel therapeutic target for sorafenib-resistant HCC patients.

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Mitophagy: A crucial modulator in the pathogenesis of chronic diseases

Cited by 34 publications

References 102 publications

Crosstalks between inflammasome and autophagy in cancer

Crosstalks between inflammasome and autophagy in cancer

Mitophagy Promotes Sorafenib Resistance through Hypoxia-Inducible ATAD3A Dependent Axis

Mitophagy Promotes Sorafenib Resistance Through a Hypoxia-Inducible ATAD3A Dependent Axis

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