Reciprocity in ROS and autophagic signaling

Wible, Daric J.; Bratton, Shawn B.

doi:10.1016/j.cotox.2017.10.006

Cited by 61 publications

(38 citation statements)

References 67 publications

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“…Here, we showed that S. pn - secreted H 2 O 2 alone was able to induce mitochondrial oxidative damage, impairing mtDNA replication and decreasing mtDNA content in lung cells. Moreover, H 2 O 2 is a type of reactive oxygen species (ROS), and as such, is an important signaling molecule that mediates oxidative stress and cellular damage (Wible and Bratton, 2018). Previous studies on intestinal health have revealed that H 2 O 2 upregulated intracellular and mitochondrial ROS expression (Jiang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

Gao

Dou

et al. 2019

Front. Microbiol.

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Streptococcus pneumoniae (S. pn) , the bacterial pathogen responsible for invasive pneumococcal diseases, is capable of producing substantial amounts of hydrogen peroxide. However, the impact of S. pn -secreted hydrogen peroxide (H 2 O 2 ) on the host immune processes is not completely understood. Here, we demonstrated that S. pn -secreted H 2 O 2 caused mitochondrial damage and severe histopathological damage in mouse lung tissue. Additionally, S. pn -secreted H 2 O 2 caused not only oxidative damage to mitochondrial deoxyribonucleic acid (mtDNA), but also a reduction in the mtDNA content in alveolar epithelia cells. This resulted in the release of mtDNA into the cytoplasm, which subsequently induced type I interferons (IFN-I) expression. We also determined that stimulator of interferon genes (STING) signaling was probably involved in S. pn H 2 O 2 -inducing IFN-I expression in response to mtDNA damaged by S. pn -secreted H 2 O 2 . In conclusion, our study demonstrated that H 2 O 2 produced by S. pn resulted in mtDNA leakage from damaged mitochondria and IFN-I production in alveolar epithelia cells, and STING may be required in this process, and this is a novel mitochondrial damage mechanism by which S. pn potentiates the IFN-I cascade in S. pn infection.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

Gao

Dou

et al. 2019

Front. Microbiol.

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“…Which was then followed by nucleation, autophagic body formation, and fused with the lysosome, and then mitophagy was completed. Abnormal mitochondria were removed timely, and cell survival was promoted [13] . Another mechanism that has been researched at present is the HIF-1α/BNIP3 / BNIP3L pathway, the increase of ROS promotes the expression of HIF-1α and HIF-1α activates the autophagy signal of downstream BNIP3/BNIP3L gene transcription.…”

Section: Discussionmentioning

confidence: 99%

The Effect of CCCP on Mitophagy in CD4+CD25+ Regulatory T Cells in Human Peripheral Blood

Yang

Karim

Yuan

et al. 2020

Preprint

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Abstract Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified, and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4+CD25+Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the ROS level gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis. When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality decreased significantly.

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“…Rhes will eliminate damaged mitochondria via mitophagy, further enhancing the mitochondrial biogenesis process. However, the continued exposure to 3-NP damages the newly born mitochondria, generating more ROS and neuronal death [43]. Hence, excessive mitophagy might promote ROS generation because Rhes works in a positive feedback loop in which it promotes mitophagy as well as produces ROS due to the damage of residual and newly formed mitochondria by 3-NP.…”

Section: Excessive Mitophagy and Mitochondrial Biogenesismentioning

confidence: 99%

Exaggerated mitophagy: a weapon of striatal destruction in the brain?

Subramaniam

2020

Biochemical Society Transactions

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Mechanisms responsible for neuronal vulnerability in the brain remain unclear. Striatal neurons are preferentially damaged by 3-nitropropionic acid (3-NP), a mitochondrial complex-II inhibitor, causing striatal damage reminiscent of Huntington's disease (HD), but the mechanisms of the selectivity are not as well understood. We have discovered that Rhes, a protein enriched in the striatum, removes mitochondria via the mitophagy process. The process becomes intensified in the presence of 3-NP, thereby eliminating most of the mitochondria from the striatum. We put forward the hypothesis that Rhes acts as a ‘mitophagy ligand' in the brain and promotes mitophagy via NIX, a mitophagy receptor. Since Rhes interacts and promotes toxicity in association with mutant huntingtin (mHTT), the genetic cause of HD, it is tempting to speculate on whether the exaggerated mitophagy may be a contributing factor to the striatal lesion found in HD. Thus, Rhes-mediated exaggerated mitophagy may act as a weapon of striatal destruction in the brain.

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Reciprocity in ROS and autophagic signaling

Cited by 61 publications

References 67 publications

Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

The Effect of CCCP on Mitophagy in CD4+CD25+ Regulatory T Cells in Human Peripheral Blood

Exaggerated mitophagy: a weapon of striatal destruction in the brain?

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