The Role of Mitochondrial Oxidative Stress and ATP Depletion in the Pathology of Manganese Toxicity

2012 ◽  
pp. 591-606 ◽  
Author(s):  
Thomas E. Gunter ◽  
Claire E. Gavin ◽  
Karlene K. Gunter
Keyword(s):  
Oxidative Stress ◽  
Manganese Toxicity ◽  
Atp Depletion ◽  
Mitochondrial Oxidative Stress

Abstract 125: Perturbation of Mitochondrial Calcium Uniporter Promotes Cardiac Oxidative Stress and Autophagy During Heart Failure

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sudarsan Rajan ◽  
Santhanam Shanmughapriya ◽  
Dhanendra Tomar ◽  
Zhiwei Dong ◽  
Joseph Y Cheung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Mouse Model ◽  
Atp Depletion ◽  
Regulatory Role ◽  
Mitochondrial Calcium ◽  
Mitochondrial Bioenergetics ◽  
Complex Assembly ◽  
New Findings

Mitochondrial calcium ([Ca 2+ ] m ) is essential for cardiomyocyte viability, and aberration of [Ca 2+ ] m is known to elicit multiple cardiac stress conditions associated with ATP depletion, reactive oxygen species, and mitochondrial permeability transition pore opening, all of which can lead to metabolic stress and the loss of dysfunctional mitochondria by aberrant autophagy. Elucidating the regulatory role of m itochondrial c alcium u niporter (MCU)-mediated [Ca 2+ ] m in modulating cardiac mitochondrial bioenergetics and autophagy has high significance and clinical impact for many pathophysiological processes. [Ca 2+ ] m is exquisitely controlled by the inner mitochondrial membrane uniporter, transporters, regulators and exchangers including MCU, MCUR1, EMRE, MICU1, MICU2 and LETM1. Our recently published findings revealed that Mitochondrial Ca 2+ Uniporter Regulator 1 (MCUR1) serves as a scaffold factor for uniporter complex assembly. We found that deletion of MCUR1 impaired [Ca 2+ ] m uptake, mitochondrial Ca 2+ current ( I MCU ) and mitochondrial bioenergetics and is associated with increased autophagy. Our new findings indicate that the impairment of [Ca 2+ ] m uptake exacerbated autophagy following ischemia-reperfusion (I/R) injury. In support of our mouse model, human failing hearts show that MCUR1 protein levels are markedly decreased and autophagy markers are increased, demonstrating a crucial link between [Ca 2+ ] m uptake and autophagy during heart failure. Additionally, our results reveal that either oxidation or disruption of human MCU Cys-97 (in mouse Cys-96; gain-of-function MCU C96A mutant) produces a conformational change within the N terminal β-grasp fold of MCU which promotes higher-order MCU complex assembly and increased I MCU activity and mitochondrial ROS levels. The results of our studies using a novel cardiac-specific MCUR1-KO model and a constitutively active global MCU C96A KI mouse model (CRISPR-Cas9 genome edited) elucidate the regulatory role of [Ca 2+ ] m in cardiac bioenergetics and autophagy during oxidative stress and myocardial infarction. Thus, targeting assembly and the activity of MCU complex will offer a new potential therapeutic target in the treatment of cardiomyopathy and heart failure.

scholarly journals Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder

2017 ◽  
Vol Volume 13 ◽  
pp. 1633-1645 ◽  
Author(s):  
Xiaosong Bu ◽  
De Wu ◽  
Xiaomei Lu ◽  
Li Yang ◽  
Xiaoyan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Autistic Spectrum Disorder ◽  
Spectrum Disorder ◽  
Mitochondrial Oxidative Stress ◽  
Autistic Spectrum

scholarly journals Role of Olive Oil and Monounsaturated Fatty Acids in Mitochondrial Oxidative Stress and Aging

2006 ◽  
Vol 64 (10) ◽  
pp. 31-39 ◽  
Author(s):  
José L. Quiles ◽  
Gustavo Barja ◽  
Maurizio Battino ◽  
José Mataix ◽  
Vincenzo Solfrizzi
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Olive Oil ◽  
Monounsaturated Fatty Acids ◽  
Mitochondrial Oxidative Stress

scholarly journals The role of mitochondrial oxidative stress in the metabolic alterations in diet‐induced obesity in rats

2019 ◽  
Vol 33 (11) ◽  
pp. 12060-12072 ◽  
Author(s):  
Gema Marín‐Royo ◽  
Cristina Rodríguez ◽  
Aliaume Le Pape ◽  
Raquel Jurado‐Lopez ◽  
María Luaces ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Oxidative Stress ◽  
Metabolic Alterations ◽  
Diet Induced Obesity

scholarly journals Exacerbated Responses to Oxidative Stress by an Na+Load in Isolated Nerve Terminals: the Role of ATP Depletion and Rise of [Ca2+]i

2000 ◽  
Vol 20 (6) ◽  
pp. 2094-2103 ◽  
Author(s):  
Christos Chinopoulos ◽  
Laszlo Tretter ◽  
Adrienn Rozsa ◽  
Vera Adam-Vizi
Keyword(s):  
Oxidative Stress ◽  
Atp Depletion ◽  
Nerve Terminals

Role of mitochondrial oxidative stress in the apoptosis induced by diospyrin diethylether in human breast carcinoma (MCF-7) cells

2008 ◽  
Vol 320 (1-2) ◽  
pp. 185-195 ◽  
Author(s):  
Binod Kumar ◽  
Amit Kumar ◽  
B. N. Pandey ◽  
K. P. Mishra ◽  
Banasri Hazra
Keyword(s):  
Oxidative Stress ◽  
Breast Carcinoma ◽  
Human Breast Carcinoma ◽  
Human Breast ◽  
Mitochondrial Oxidative Stress ◽  
Mcf 7

Mitochondrial Oxidative Stress-Induced Epigenetic Modif ications in Pancreatic Epithelial Cells

2014 ◽  
Vol 33 (2) ◽  
pp. 116-129 ◽  
Author(s):  
Pradyumna Kumar Mishra ◽  
Gorantla Venkata Raghuram ◽  
Deepika Jain ◽  
Subodh Kumar Jain ◽  
Naveen Kumar Khare ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Fragile Sites ◽  
Gene Promoters ◽  
Mitochondrial Oxidative Stress ◽  
Altered Expression ◽  
Posttranslational Histone Modifications

Emerging studies have linked prooxidative carbamate compound exposures with various human pathologies including pancreatic cancer. In these studies, our aim was to examine mitochondrial oxidative stress-mediated aberrant chromatin responses in human pancreatic ductal epithelial cells. Posttranslational histone modifications, promoter DNA methylation, and micro-RNA (miRNA) expression patterns were evaluated following induction of mitochondrial oxidative stress by N-succinimidyl N-methylcarbamate exposure. In treated cells, perturbation in mitochondrial machinery led to hypermethylation of p16 and smad4 gene promoters and downregulation of respective gene products. Posttranslational histone modifications that include hypoacetylation of acetylated histone (AcH) 3 and AcH4, hypermethylation of monomethylated histone 3 at lysine 9 and trimethylated histone 4 at lysine 20 ubiquitinated histone (uH) 2A/uH2B, and increased phosphorylation of H2AX and H3 were observed in the treated cells. Altered expression of miRNAs denoted possible location of corresponding genes at oxidatively damaged fragile sites. Collectively, our results provide a direct role of mitochondrial oxidative stress-mediated epigenetic imbalance to perturbed genomic integrity in oxygen radical-induced pancreatic injury. Further, identification and characterization of molecular switches that affect these epigenomic signatures and targets thereof will be imperative to understand the complex role of redox-regulatory network in pancreatic milieu.

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