Mitochondria autophagy: a potential target for cancer therapy

Qiu, Yuhan; Wang, Xiaowei; Wang, Meng-Yan; Zhao, Wenxia; Zhou, Huimin; Zhang, Cong-Hui; Cai, Meilian; Chen, Xiaofang; Zhao, Wei; Shao, Rong‐Guang

doi:10.1080/1061186x.2020.1867992

Cited by 29 publications

(26 citation statements)

References 158 publications

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“…Recent research reported that NRF2 may be associated with mitophagy, and that the function of NRF2 in mitophagy may involve the PINK1/PRKN pathway. 42 In the present study, we identified NRF2 activation in vitro model of S-AKI. Our in vitro studies showed that NRF2 inhibition of LPS-treated cells further exacerbated cell injury.…”

Section: Discussionmentioning

confidence: 73%

“…Recent research reported that NRF2 may be associated with mitophagy, and that the function of NRF2 in mitophagy may involve the PINK1/PRKN pathway. 42 In the present study, we iden- Mitochondrial dysfunction is the main cause of sepsis-induced organ failure and is closely related to patient prognosis. 43 Mitochondrial damage occurs during S-AKI, thus mitochondrial protection strategies may be key to the prevention and treatment of S-AKI.…”

Section: Discussionmentioning

confidence: 91%

“… 25 To maintain a healthy mitochondrial population, an appropriate balance between mitophagy and mitochondria biogenesis is necessary. 42 Other studies also reported a relationship between NRF2 and mitochondrial biogenesis. 59 , 60 In addition to NRF1, these studies found that NRF2 was also involved in the regulation of PGC1-a in maintaining mitochondrial biogenesis, which becomes predominant under conditions of stress.…”

Section: Discussionmentioning

confidence: 93%

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Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) ameliorates sepsis-associated acute kidney injury by maintaining mitochondrial homeostasis and improving the mitochondrial function

Chen

Wang

et al. 2022

Eur J Histochem

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Mitochondrial dysfunction has a role in sepsis-associated acute kidney injury (S-AKI), so the restoration of normal mitochondrial homeostasis may be an effective treatment strategy. Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) is a main regulator of cell-redox homeostasis, and recent studies reported that NRF2 activation helped to preserve mitochondrial morphology and function under conditions of stress. However, the role of NRF2 in the process of S-AKI is still not well understood. The present study investigated whether NRF2 regulates mitochondrial homeostasis and influences mitochondrial function in S-AKI. We demonstrated activation of NRF2 in an in vitro model: lipopolysaccharide (LPS) challenge of ductal epithelial cells of rat renal tubules (NRK-52e cells), and an in vivo model: cecal ligation and puncture (CLP) of rats. Over-expression of NRF2 attenuated oxidative stress, apoptosis, and the inflammatory response; enhanced mitophagy and mitochondrial biogenesis; and mitigated mitochondrial damage in the in vitro model. In vivo experiments showed that rats treated with an NRF2 agonist had higher adenosine triphosphate (ATP) levels, lower blood urea nitrogen and creatinine levels, fewer renal histopathological changes, and higher expression of mitophagy-related proteins [PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PRKN), microtubule-associated protein 1 light chain 3 II (LC3 II)] and mitochondrial biogenesis-related proteins [peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) and mitochondrial transcription factor A (TFAM)]. Electron microscopy of kidney tissues showed that mitochondrial damage was alleviated by treatment with an NRF2 agonist, and the opposite response occurred upon treatment with an NRF2 antagonist. Overall, our findings suggest that mitochondria have an important role in the pathogenesis of S-AKI, and that NRF2 activation restored mitochondrial homeostasis and function in the presence of this disease. This mitochondrial pathway has the potential to be a novel therapeutic target for the treatment of S-AKI.

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Section: Discussionmentioning

confidence: 73%

“…Recent research reported that NRF2 may be associated with mitophagy, and that the function of NRF2 in mitophagy may involve the PINK1/PRKN pathway. 42 In the present study, we iden- Mitochondrial dysfunction is the main cause of sepsis-induced organ failure and is closely related to patient prognosis. 43 Mitochondrial damage occurs during S-AKI, thus mitochondrial protection strategies may be key to the prevention and treatment of S-AKI.…”

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) ameliorates sepsis-associated acute kidney injury by maintaining mitochondrial homeostasis and improving the mitochondrial function

Chen

Wang

et al. 2022

Eur J Histochem

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“…In some studies, mitophagy increases cancer cell sensitivity to chemotherapy by maintaining cellular homeostasis and preventing oncogenic transformation ( 51 ). In contrast, mitophagy promotes cancer cell survival and confers cell resistance to chemotherapeutic stress by degrading damaged mitochondria and reducing mitochondrial reactive oxygen species ( 52 ). In our research, a mitophagy inhibitor significantly improved the sensitivity of PIWIL1-overexpressing MM cells to chemotherapeutic drugs, validating the role of mitophagy in inducing MM chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population

et al. 2022

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As an important member of the Argonaute protein family, PIWI-like protein 1 (PIWIL1) plays a key role in tumor cell viability. However, the exact function of PIWIL1 in multiple myeloma (MM) and the underlying mechanism remain unclear. Here, we revealed that PIWIL1 was highly expressed in myeloma cell lines and newly diagnosed MM patients, and that its expression was notably higher in refractory/relapsed MM patients. PIWIL1 promoted the proliferation of MM cells and conferred resistance to chemotherapeutic agents both in vitro and in vivo. More importantly, PIWIL1 enhanced the formation of autophagosomes, especially mitophagosomes, by disrupting mitochondrial calcium signaling and modulating mitophagy-related canonical PINK1/Parkin pathway protein components. Mitophagy/autophagy inhibitors overcome PIWIL1-induced chemoresistance. In addition, PIWIL1 overexpression increased the proportion of side population (SP) cells and upregulated the expression of the stem cell-associated genes Nanog, OCT4, and SOX2, while its inhibition resulted in opposite effects. Taken together, our findings demonstrated that PIWIL1 induced drug resistance by activating mitophagy and regulating the MM stem cell population. PIWIL1 depletion significantly overcame drug resistance and could be used as a novel therapeutic target for reversing resistance in MM patients.

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“…Regarding tumorigenesis, autophagy seems to play a dual role based on the cancer type, stage and genetic background of the patient. Initially, autophagy acts as a tumor suppressor by decreasing oncogenic protein p62 and assists in eliminating impaired organelles or DNA to impede further cellular damage and malignancy development[ 23 , 24 ]. Subsequently, autophagy can protect tumors from damages triggered by nutrient shortage, radiation and chemotherapeutics and strengthen tumor immune escape, metabolism and growth, resulting in drug resistance[ 23 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Role of autophagy in gastric carcinogenesis

Papaefthymiou

Christodoulidis

Koffas

et al. 2021

WJGO

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Gastric cancer represents a common and highly fatal malignancy, and thus a pathophysiology-based reconsideration is necessary, given the absence of efficient therapeutic regimens. In this regard, emerging data reveal a significant role of autophagy in gastric oncogenesis, progression, metastasis and chemoresistance. Although autophagy comprises a normal primordial process, ensuring cellular homeostasis under energy depletion and stress conditions, alterations at any stage of the complex regulatory system could stimulate a tumorigenic and promoting cascade. Among others, Helicobacter pylori infection induces a variety of signaling molecules modifying autophagy, during acute infection or after chronic autophagy degeneration. Subsequently, defective autophagy allows malignant transformation and upon cancer establishment, an overactive autophagy is stimulated. This overexpressed autophagy provides energy supplies and resistance mechanisms to gastric cancer cells against hosts defenses and anticancer treatment. This review interprets the implicated autophagic pathways in normal cells and in gastric cancer to illuminate the potential preventive, therapeutic and prognostic benefits of understanding and intervening autophagy.

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Mitochondria autophagy: a potential target for cancer therapy

Cited by 29 publications

References 158 publications

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) ameliorates sepsis-associated acute kidney injury by maintaining mitochondrial homeostasis and improving the mitochondrial function

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) ameliorates sepsis-associated acute kidney injury by maintaining mitochondrial homeostasis and improving the mitochondrial function

PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population

Role of autophagy in gastric carcinogenesis

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