scholarly journals TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight

Redox Biology ◽  
2018 ◽  
Vol 15 ◽  
pp. 266-276 ◽  
Author(s):  
Qun Chen ◽  
Ningning Wang ◽  
Mingjiang Zhu ◽  
Jianhong Lu ◽  
Huiqin Zhong ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Tio2 Nanoparticles ◽  
Inflammatory Responses

scholarly journals Type I interferon potentiates metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice

2020 ◽  
Author(s):  
Yuanjiu Lei ◽  
Camila Guerra Martinez ◽  
Sylvia Torres-Odio ◽  
Samantha L. Bell ◽  
Christine E. Birdwell ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Aerobic Glycolysis ◽  
Accelerated Aging ◽  
Innate Immune ◽  
Related Factor ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Polymerase Gamma

AbstractMitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune crosstalk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA (mtDNA) instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces healthspan, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increases oxidative stress, enhances pro-inflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyper-inflammatory phenotypes by restoring Nrf2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related diseases and aging.

scholarly journals Echinacoside Protects against 6-Hydroxydopamine-Induced Mitochondrial Dysfunction and Inflammatory Responses in PC12 Cells via Reducing ROS Production

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yue-Hua Wang ◽  
Zhao-Hong Xuan ◽  
Shuo Tian ◽  
Guan-Hua Du
Keyword(s):  
Mitochondrial Dysfunction ◽  
Pc12 Cells ◽  
Inflammatory Responses ◽  
Neurodegenerative Disorder ◽  
Cell Damage ◽  
Underlying Mechanism ◽  
Ros Production ◽  
Neuroprotective Effects ◽  
Reduction Activity ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. Mitochondrial dysfunction and inflammatory responses are involved in the mechanism of cell damage in PD. 6-Hydroxydopamine (6-OHDA), a dopamine analog, specifically damages dopaminergic neurons. Echinacoside (ECH) is a phenylethanoid glycoside isolated from the stems ofCistanche salsa, showing a variety of neuroprotective effects in previous studies. The present study was to investigate its effect against 6-OHDA-induced neurotoxicity and possible mechanisms in PC12 cells. The results showed that 6-OHDA reduced cell viability, decreased oxidation-reduction activity, decreased mitochondrial membrane potential, and induced mitochondria-mediated apoptosis compared with untreated PC12 cells. However, echinacoside treatment significantly attenuated these changes induced by 6-OHDA. In addition, echinacoside also could significantly alleviate the inflammatory responses induced by 6-OHDA. Further research showed that echinacoside could reduce 6-OHDA-induced ROS production in PC12 cells. These results suggest that the underlying mechanism of echinacoside against 6-OHDA-induced neurotoxicity may be involve in attenuating mitochondrial dysfunction and inflammatory responses by reducing ROS production.

scholarly journals Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonia Shastri ◽  
Tanvi Shinde ◽  
Krystel L. Woolley ◽  
Jason A. Smith ◽  
Nuri Gueven ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Critical Role ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Sodium Sulphate ◽  
Short Chain ◽  
Cytokines And Chemokines

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

scholarly journals Mitophagy and Mitochondrial Dysfunction in Cancer

2020 ◽  
Vol 4 (1) ◽  
pp. 41-60 ◽  
Author(s):  
Kay F. Macleod
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cell Fate ◽  
Inflammatory Responses ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Tumor Cell Growth ◽  
Mitochondrial Mass ◽  
Cell Fate Decisions ◽  
Signaling Mechanisms ◽  
Altered Cell

The process of mitophagy, in which mitochondria are selectively turned over at the autophagolysosome, plays a central role in both eliminating dysfunctional mitochondria and reducing mitochondrial mass as an adaptive response to key physiological stresses, such as hypoxia, nutrient deprivation, and DNA damage. Defects in mitophagy have been linked to altered mitochondrial metabolism, production of excess reactive oxygen species and ferroptosis, heightened inflammasome activation, altered cell fate decisions, and senescence, among other cellular consequences. Consequently, functional mitophagy contributes to proper tissue differentiation and repair and metabolic homeostasis, limiting inflammatory responses and modulating tumor progression and metastasis. This review examines the major pathways that control mitophagy, including PINK1-dependent mitophagy and BNIP3/NIX-dependent mitophagy. It also discusses the cellular signaling mechanisms used to sense mitochondrial dysfunction to activate mitophagy and how defective mitophagy results in deregulated tumor cell growth and cancer.

scholarly journals 088 MITOCHONDRIAL DYSFUNCTION PROMOTES PRO-INFLAMMATORY RESPONSES IN CULTURED NORMAL HUMAN SYNOVIOCYTES

2010 ◽  
Vol 18 ◽  
pp. S46-S47
Author(s):  
M.N. Valcárcel-Ares ◽  
R.R. Riveiro-Naveira ◽  
C. Vaamonde-Garcia ◽  
F.J. Blanco ◽  
M.J. López-Armada
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Normal Human

scholarly journals Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice

2021 ◽  
Vol 7 (22) ◽  
pp. eabe7548
Author(s):  
Yuanjiu Lei ◽  
Camila Guerra Martinez ◽  
Sylvia Torres-Odio ◽  
Samantha L. Bell ◽  
Christine E. Birdwell ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Aerobic Glycolysis ◽  
Accelerated Aging ◽  
Innate Immune ◽  
Related Factor ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Elevated Type

Mitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune cross-talk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces health span, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2–related factor 2 (NRF2), which increases oxidative stress, enhances proinflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyperinflammatory phenotypes by restoring NRF2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related disorders and aging.

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