Temporal evolution of cardiac mitochondrial dysfunction in a type 1 diabetes model. Mitochondrial complex I impairment, and H2O2 and NO productions as early subcellular events

2021 ◽  
Vol 162 ◽  
pp. 129-140
Author(s):  
Ivana A. Rukavina-Mikusic ◽  
Micaela Rey ◽  
Manuela Martinefski ◽  
Valeria Tripodi ◽  
Laura B. Valdez
Keyword(s):  
Type 1 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Temporal Evolution ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Diabetes Model

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Inhibition of Mitochondrial Complex I Aggravates Folic Acid-Induced Acute Kidney Injury

2019 ◽  
Vol 44 (5) ◽  
pp. 1002-1013 ◽  
Author(s):  
Wen Zhang ◽  
Yunwen Yang ◽  
Huiping Gao ◽  
Yue Zhang ◽  
Zhanjun Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Folic Acid ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Kidney Injury ◽  
Mitochondrial Complex I ◽  
Tubular Injury ◽  
Mitochondrial Complex ◽  
Renal Tubular

Background: Some researches revealed that mitochondrial dysfunction is associated with various kidney injury. However, the role of mitochondrial dysfunction in the pathogenesis of acute kidney injury (AKI) still needs evidence. Methods: We evaluated the effect of mitochondrial complex I inhibitor rotenone on folic acid (FA)-induced AKI in mice. Results: Strikingly, the mice pretreated with rotenone at a dose of 200 ppm in food showed exacerbated kidney injury as shown by higher levels of blood urea nitrogen and creatinine compared with FA alone group. Meanwhile, both renal tubular injury score and the expression of renal tubular injury marker neutrophil gelatinase-associated lipocalin were further elevated in rotenone-pretreated mice, suggesting the deteriorated renal tubular injury. Moreover, the decrements of mitochondrial DNA copy number and the expressions of mitochondrial Cytochrome c oxidase subunit 1, mitochondrial NADH dehydrogenase subunit 1, and mitochondria-specific superoxide dismutase (SOD2) in the kidneys of FA-treated mice were further reduced in rotenone-pretreated mice, indicating the aggravated mitochondrial damage. In parallel with the SOD2 reduction, the oxidative stress markers of malondialdehyde and HO-1 displayed greater increment in AKI mice with rotenone pretreatment in line with the deteriorated apoptotic response and inflammation. Conclusion: Our results suggested that the inhibition of mitochondrial complex I activity aggravated renal tubular injury, mitochondrial damage, oxidative stress, cell apoptosis, and inflammation in FA-induced AKI.

scholarly journals Epigallocatechin-3-Gallate Plus Omega-3 Restores the Mitochondrial Complex I and F0F1-ATP Synthase Activities in PBMCs of Young Children with Down Syndrome: A Pilot Study of Safety and Efficacy

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 469
Author(s):  
Iris Scala ◽  
Daniela Valenti ◽  
Valentina Scotto D’Aniello ◽  
Maria Marino ◽  
Maria Pia Riccio ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mitochondrial Dysfunction ◽  
Atp Synthase ◽  
Complex I ◽  
Antioxidant Properties ◽  
Control Group ◽  
Mitochondrial Complex I ◽  
Omega 3 ◽  
Mitochondrial Complex ◽  
F0f1 Atp Synthase

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Epigallocatechin-3-gallate (EGCG) is a multimodal nutraceutical with antioxidant properties. EGCG inhibits DYRK1A overexpression and corrects DS mitochondrial dysfunction in vitro. The present study explores safety profiles in DS children aged 1–8 years treated with EGCG (10 mg/kg/die, suspended in omega-3, per os, in fasting conditions, for 6 months) and EGCG efficacy in restoring mitochondrial complex I and F0F1-ATP synthase (complex V) deficiency, assessed on PBMCs. The Griffiths Mental Developmental Scales—Extended Revised (GMDS-ER) was used for developmental profiling. Results show that decaffeinated EGCG (>90%) plus omega-3 is safe in DS children and effective in reverting the deficit of mitochondrial complex I and V activities. Decline of plasma folates was observed in 21% of EGCG-treated patients and should be carefully monitored. GMDS-ER scores did not show differences between the treated group compared to the DS control group. In conclusion, EGCG plus omega-3 can be safely administered under medical supervision in DS children aged 1–8 years to normalize mitochondria respiratory chain complex activities, while results on the improvement of developmental performance are still inconclusive.

Rabies virus phosphoprotein interacts with mitochondrial Complex I and induces mitochondrial dysfunction and oxidative stress

2015 ◽  
Vol 21 (4) ◽  
pp. 370-382 ◽  
Author(s):  
Wafa Kammouni ◽  
Heidi Wood ◽  
Ali Saleh ◽  
Camila M. Appolinario ◽  
Paul Fernyhough ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Rabies Virus ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
And Oxidative Stress

scholarly journals Mitochondrial Dysfunction and Cellular Senescence Due to Aging Contributes to Prostatic Fibrosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 133-134
Author(s):  
Teresa Liu ◽  
Emily Ricke ◽  
Donald DeFranco ◽  
William Ricke
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cellular Senescence ◽  
Mitochondrial Function ◽  
Complex I ◽  
Molecular Mechanisms ◽  
Selective Inhibition ◽  
Urinary Symptoms ◽  
Lower Urinary Tract Dysfunction ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex

Abstract Aging is the single largest risk factor for many common diseases that burden public health. This is especially true in the prostate; as men age, the prostate undergoes a prototypical aging change, fibrosis. The aged fibrotic prostate causes urinary symptoms which will afflict nearly every man if they live long enough. However, the molecular mechanisms responsible for the aging-dependent promotion of fibrosis are largely unknown and understudied. In this study, we sought to reveal the contribution of mitochondrial dysfunction to fibrosis in the aging prostate, ultimately leading to prostate dysfunction, urinary symptoms, and overall poor health. The demise of mitochondrial function is well established in other aging-associated diseases but has not been investigated in the prostate. Our analysis revealed an increase in cellular senescence and mitochondrial dysfunction in BPH patient tissue compared to normal prostates. Furthermore, selective inhibition of mitochondrial complex I by rotenone in cultured human prostate fibroblasts led to myofibroblast phenoconversion as characterized by increased expression of Col1a1, Col3a1, and ACTA2. To determine the contribution of mitochondrial dysfunction on fibrosis and lower urinary tract dysfunction (LUTD), we examined the prostate lobes in both aging and steroid-induced LUTD in mice. These models have been extensively characterized and exhibit an age-mediated increase in LUTD and fibrosis. We observed a decrease in mitochondrial function and an increase in cellular senescence corresponding to an increase in fibrosis and LUTD. This suggests that normal aging-dependent reductions in mitochondrial complex I function in the prostate may promote fibrosis and contribute to urinary dysfunction.

ATP-Sensitive Potassium Channels in Dopaminergic Neurons: Transducers of Mitochondrial Dysfunction

Physiology ◽  
2001 ◽  
Vol 16 (5) ◽  
pp. 214-217 ◽  
Author(s):  
Birgit Liss ◽  
Jochen Roeper
Keyword(s):  
Electrical Activity ◽  
Mitochondrial Dysfunction ◽  
Dopaminergic Neurons ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Midbrain Neurons ◽  
Channel Expression ◽  
A Cell ◽  
Complex I Activity

ATP-sensitive potassium (KATP) channels directly couple the metabolic state of a cell to its electrical activity. Dopaminergic midbrain neurons express alternative types of KATP channels mediating their differential response to mitochondrial complex I inhibition. Because reduced complex I activity is present in Parkinson's Disease, differential KATP channel expression suggests a novel candidate mechanism for selective dopaminergic degeneration.

Sign in / Sign up

Export Citation Format

Share Document