Bcl-2 Proteins Regulate Mitophagy in Lipopolysaccharide-Induced Acute Lung Injury via PINK1/Parkin Signaling Pathway

Zhang, Zhihao; Chen, Zhugui; Liu, Ruimeng; Liang, Qingchun; Peng, Zhiyong; Yin, Shaowu; Tang, Jing; Gong, Ting; Liu, Youtan

doi:10.1155/2020/6579696

Cited by 31 publications

(38 citation statements)

References 54 publications

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“…Overexpression of pro-survival BCL-2 family proteins, and specifically BCL-x L , in cultured cell lines has been shown to inhibit Parkin translocation to the OMM (Hollville et al 2014;Yu et al 2020;Zhang et al 2020). This seems contradictory to the pro-survival role of BCL-x L , as this would decrease the amount of mitophagy, thereby increasing the risk of dysfunctional mitochondria generating ROS.…”

Section: Influence Of Bcl-2 Family Proteins On Parkin Translocationmentioning

confidence: 99%

Kill one or kill the many: interplay between mitophagy and apoptosis

Wanderoy

Hees

Klesse

et al. 2020

Biological Chemistry

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Mitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson’s disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of pro-apoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.

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Section: Influence Of Bcl-2 Family Proteins On Parkin Translocationmentioning

confidence: 99%

Kill one or kill the many: interplay between mitophagy and apoptosis

Wanderoy

Hees

Klesse

et al. 2020

Biological Chemistry

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“…However, excessive mitophagy may promote mitochondrial dysfunction and cause cell injury and death [ 37 ]. For example, it has been reported that mitophagy contributes to increased inflammation and lung injury in ALI [ 36 , 38 ]. During ALI, the activation of mitophagy plays a critical role in the production of proinflammatory cytokines including TNF- α , IL-1 β , and IL-6 and these cytokines all play important roles in the progress of ALI [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been reported that Parkin-Pink1-mediated mitophagy contributes to necroptosis and pathology in chronic obstructive pulmonary disease (COPD) [ 37 ]. During ALI, Parkin/Pink1-mediated mitophagy contributes to inflammation [ 36 ]. In consistency with these studies, we discovered that oxyberberine prevented LPS-induced ALI through inhibition of mitophagy.…”

Section: Discussionmentioning

confidence: 99%

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Oxyberberine Prevented Lipopolysaccharide‐Induced Acute Lung Injury through Inhibition of Mitophagy

Zhao

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Acute lung injury (ALI) is a serious respiratory syndrome characterized with uncontrolled inflammatory response. Oxyberberine has strong potential for clinical usage since it showed strong anti-inflammatory, antifungal, and antiarrhythmic effects in various diseases. In the present study, we evaluated whether oxyberberine can inhibit lipopolysaccharide- (LPS-) induced ALI in vivo and further evaluated the possible involvement of mitophagy in vitro by using A549 cells, a human lung epithelial cell line. Our in vivo study shows that oxyberberine significantly inhibited LPS-induced lung pathological injury and lung edema, as indicated by the changes in lung wet/dry ratio and total protein levels in the BALF in mice. Moreover, oxyberberine inhibited inflammation, as indicated by the changes of neutrophil accumulation and production of proinflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 in both the lung and bronchoalveolar lavage fluid (BALF) in ALI mice. Our in vitro study shows that LPS significantly decreased the protein level of mitochondrial proteins, including cytochrome c oxidase subunit IV (COX IV), p62, and mitofusin-2 (Mfn2) in A549 cells. In addition, LPS induced significant Parkin1 translocation from cytoplasm to mitochondria. These changes were significantly inhibited by oxyberberine. Notably, the inhibitory effect of oxyberberine was almost totally lost in the presence of lysosome fusion inhibitor bafilomycin A1 (Baf), a mitophagy inhibitor. In conclusion, the present study demonstrated that oxyberberine alleviated LPS-induced inflammation in ALI via inhibition of Parkin-mediated mitophagy.

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“…Lipopolysaccharide (LPS) is the component of outer cell wall of gram-negative bacteria, which is the main pathogenic substance in sepsis-induced lung injury. And researches have shown that LPS-induced lung epithelial cell injury can be simulated in vivo in sepsis lung injury ( Su et al, 2012 ; Zhang et al, 2020 ). Thus, to determine the protective effect of TP on alveolar epithelium, L2 cells, one kind of alveolar epithelial cell lines, were treated with 100 ng/mL LPS.…”

Section: Discussionmentioning

confidence: 99%

Tea Polyphenols Prevent Sepsis-Induced Lung Injury via Promoting Translocation of DJ-1 to Mitochondria

Chen¹,

Zhang²,

Wang³

et al. 2021

Front. Cell Dev. Biol.

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BackgroundSepsis is the systemic inflammatory response syndrome caused by infection, which commonly targets on the lung. Tea polyphenols (TP) have many pharmacological activities, but their role in sepsis induced lung injury remains unclear.ResultsInjection of TP after cecal ligation and puncture (CLP) operation elevated the survival rate in a concentration dependent manner. TP treatment improved alveoli structure injury under CLP operation. CLP surgery increased the expression of inflammatory factors IL1β, IL6, and TNFα expression, which was reversed by TP injection. In addition, CLP operation promoted apoptosis and senescence in tissues and cells during lung injury, while TP administration removed the damaged role of CLP on lung tissues and cells. Furthermore, CLP operation or LPS (lipopolysaccharide) treatment induced dysfunction of mitochondria in lung tissues and cells, but TP contributed to recover mitochondria function, which exhibited as inhibition of ROS production inhibition and increase of ATP content and Mitochondrial membrane potential (MMP). Interestingly, DJ-1 was inhibited by CLP operation but promoted by TP treatment. Overexpression of DJ-1 reversed the injury of LPS on L2 cells and recovered mitochondria normal function. And silencing of DJ-1 in rats or alveolar epithelial cells blocked the protection effect of TP.ConclusionOur research revealed that TP protected against lung injury via upregulating of DJ-1 to improve mitochondria function, which contributed to the prevention and treatment of sepsis induced lung injury.

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Bcl-2 Proteins Regulate Mitophagy in Lipopolysaccharide-Induced Acute Lung Injury via PINK1/Parkin Signaling Pathway

Cited by 31 publications

References 54 publications

Kill one or kill the many: interplay between mitophagy and apoptosis

Kill one or kill the many: interplay between mitophagy and apoptosis

Oxyberberine Prevented Lipopolysaccharide‐Induced Acute Lung Injury through Inhibition of Mitophagy

Tea Polyphenols Prevent Sepsis-Induced Lung Injury via Promoting Translocation of DJ-1 to Mitochondria

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