ARX-associated infantile epileptic-dyskinetic encephalopathy with responsiveness to valproate for controlling seizures and reduced activity of muscle mitochondrial complex IV

2019 ◽  
Vol 41 (10) ◽  
pp. 883-887
Author(s):  
Anna Ka-Yee Kwong ◽  
Vanessa Loi-Yan Chu ◽  
Richard J.T. Rodenburg ◽  
Jan Smeitink ◽  
Cheuk-Wing Fung
Keyword(s):  
Mitochondrial Complex ◽  
Complex Iv ◽  
Reduced Activity

scholarly journals COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2

2015 ◽  
Vol 24 (19) ◽  
pp. 5404-5415 ◽  
Author(s):  
David A. Stroud ◽  
Megan J. Maher ◽  
Caroline Lindau ◽  
F.-Nora Vögtle ◽  
Ann E. Frazier ◽  
...  
Keyword(s):  
Mitochondrial Complex ◽  
Complex Iv ◽  
Assembly Factor

scholarly journals Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anouk C. Tengeler ◽  
Tim L. Emmerzaal ◽  
Bram Geenen ◽  
Vivienne Verweij ◽  
Miranda van Bodegom ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mitochondrial Function ◽  
Adolescent Male ◽  
Mitochondrial Complex ◽  
Mitochondrial Translation ◽  
Behavioral Screening ◽  
Behavioral Deficits ◽  
Complex Iv ◽  
Marble Burying ◽  
Behavior And Cognition

AbstractExposure to antibiotic treatment has been associated with increased vulnerability to various psychiatric disorders. However, a research gap exists in understanding how adolescent antibiotic therapy affects behavior and cognition. Many antibiotics that target bacterial translation may also affect mitochondrial translation resulting in impaired mitochondrial function. The brain is one of the most metabolically active organs, and hence is the most vulnerable to impaired mitochondrial function. We hypothesized that exposure to antibiotics during early adolescence would directly affect brain mitochondrial function, and result in altered behavior and cognition. We administered amoxicillin, chloramphenicol, or gentamicin in the drinking water to young adolescent male wild-type mice. Next, we assayed mitochondrial oxidative phosphorylation complex activities in the cerebral cortex, performed behavioral screening and targeted mass spectrometry-based acylcarnitine profiling in the cerebral cortex. We found that mice exposed to chloramphenicol showed increased repetitive and compulsive-like behavior in the marble burying test, an accurate and sensitive assay of anxiety, concomitant with decreased mitochondrial complex IV activity. Our results suggest that only adolescent chloramphenicol exposure leads to impaired brain mitochondrial complex IV function, and could therefore be a candidate driver event for increased anxiety-like and repetitive, compulsive-like behaviors.

scholarly journals Non-additive interactions between mitochondrial complex IV blockers and hypoxia in rat carotid body responses

2014 ◽  
Vol 190 ◽  
pp. 62-69 ◽  
Author(s):  
David F. Donnelly ◽  
Insook Kim ◽  
Eileen M. Mulligan ◽  
John L. Carroll
Keyword(s):  
Carotid Body ◽  
Mitochondrial Complex ◽  
Complex Iv ◽  
Additive Interactions

scholarly journals The Lebanese Allele in the PET100 Gene: Report on Two New Families with Cytochrome c Oxidase Deficiency

2019 ◽  
Vol 08 (03) ◽  
pp. 172-178 ◽  
Author(s):  
Hicham Mansour ◽  
Sandra Sabbagh ◽  
Sami Bizzari ◽  
Stephany El-Hayek ◽  
Eliane Chouery ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Lactic Acidosis ◽  
Developmental Delay ◽  
Cytochrome C Oxidase ◽  
Brain Magnetic Resonance Imaging ◽  
Global Developmental Delay ◽  
Mitochondrial Complex ◽  
Oxidase Deficiency ◽  
Complex Iv ◽  
Cytochrome C Oxidase Deficiency

AbstractCytochrome c oxidase deficiency is caused by mutations in any of at least 30 mitochondrial and nuclear genes involved in mitochondrial complex IV biogenesis and structure, including the recently identified PET100 gene. Here, we report two families, of which one is consanguineous, with two affected siblings each. In one family, the siblings presented with developmental delay, seizures, lactic acidosis, abnormal brain magnetic resonance imaging, and low muscle mitochondrial complex IV activity at 30%. In the other family, the two siblings, now deceased, had a history of global developmental delay, failure to thrive, muscular hypotonia, seizures, developmental regression, respiratory insufficiency, and lactic acidosis. By whole exome sequencing, a missense mutation in exon 1 of the PET100 gene (c.3G > C; [p.Met1?]) was identified in both families. A review of the clinical description and literature is discussed, highlighting the importance of this variant in the Lebanese population.

Microencapsulated pomegranate peel extract induces mitochondrial complex IV activity and prevents mitochondrial cristae alteration in brown adipose tissue in mice fed on a high-fat diet+

2020 ◽  
pp. 1-37
Author(s):  
F Echeverria ◽  
P Jimenez ◽  
M Castro-Sepulveda ◽  
A Bustamante ◽  
P Garcia ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Mitochondrial Complex ◽  
High Fat ◽  
Pomegranate Peel ◽  
Complex Iv ◽  
Pomegranate Peel Extract ◽  
And Function ◽  
Peel Extract

Abstract Pomegranate peel is an agro-industrial residue obtained after fruit processing with high total polyphenol (TP) content, making it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favouring mitochondrial biogenesis and function have also been described. However, once phenolic compounds are extracted, their stability can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation into functional foods. Nevertheless, studies on the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. This study aims to evaluate the effect of MPPE on BAT mitochondrial structure and function and metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a wall material and physically-chemically characterized. Eight-week-old male C57BL/6J mice (n=40) were randomly distributed into five groups: control diet (CD), HFD, HFD+IN, HFD+PPE (50 mg/kg/d TP), and HFD+MPPE (50 mg/kg/d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. Blood and adipose tissue samples were obtained. MPPE supplementation prevented HFD-induced body weight gain (p<0.001), fasting glycemia (p=0.007), and total cholesterol rise (p=0.001). MPPE resulted in higher BAT mitochondrial complex IV activity (p=0.03) and prevented HFD-induced mitochondrial cristae alteration (p=0.02). In conclusion, MPPE prevented HFD-induced excessive body weight gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae structure in BAT in mice fed with an HFD.

scholarly journals Multiple pathways coordinate assembly of human mitochondrial complex IV and stabilization of respiratory supercomplexes

2020 ◽  
Vol 39 (14) ◽  
Author(s):  
Teresa Lobo‐Jarne ◽  
Rafael Pérez‐Pérez ◽  
Flavia Fontanesi ◽  
Alba Timón‐Gómez ◽  
Ilka Wittig ◽  
...  
Keyword(s):  
Mitochondrial Complex ◽  
Complex Iv ◽  
Respiratory Supercomplexes

scholarly journals Serine-70 phosphorylated Bcl-2 prevents oxidative stress-induced DNA damage by modulating the mitochondrial redox metabolism

2020 ◽  
Vol 48 (22) ◽  
pp. 12727-12745 ◽  
Author(s):  
Stephen Jun Fei Chong ◽  
Kartini Iskandar ◽  
Jolin Xiao Hui Lai ◽  
Jianhua Qu ◽  
Deepika Raman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Lines ◽  
Ros Production ◽  
Primary Cells ◽  
Mitochondrial Complex ◽  
Drug Induced ◽  
Complex Iv ◽  
Redox Sensor

Abstract Bcl-2 phosphorylation at serine-70 (S70pBcl2) confers resistance against drug-induced apoptosis. Nevertheless, its specific mechanism in driving drug-resistance remains unclear. We present evidence that S70pBcl2 promotes cancer cell survival by acting as a redox sensor and modulator to prevent oxidative stress-induced DNA damage and execution. Increased S70pBcl2 levels are inversely correlated with DNA damage in chronic lymphocytic leukemia (CLL) and lymphoma patient-derived primary cells as well as in reactive oxygen species (ROS)- or chemotherapeutic drug-treated cell lines. Bioinformatic analyses suggest that S70pBcl2 is associated with lower median overall survival in lymphoma patients. Empirically, sustained expression of the redox-sensitive S70pBcl2 prevents oxidative stress-induced DNA damage and cell death by suppressing mitochondrial ROS production. Using cell lines and lymphoma primary cells, we further demonstrate that S70pBcl2 reduces the interaction of Bcl-2 with the mitochondrial complex-IV subunit-5A, thereby reducing mitochondrial complex-IV activity, respiration and ROS production. Notably, targeting S70pBcl2 with the phosphatase activator, FTY720, is accompanied by an enhanced drug-induced DNA damage and cell death in CLL primary cells. Collectively, we provide a novel facet of the anti-apoptotic Bcl-2 by demonstrating that its phosphorylation at serine-70 functions as a redox sensor to prevent drug-induced oxidative stress-mediated DNA damage and execution with potential therapeutic implications.

Trolox protects mitochondrial complex IV from nitric oxide-mediated damage in astrocytes

1994 ◽  
Vol 668 (1-2) ◽  
pp. 243-245 ◽  
Author(s):  
Simon J.R. Heales ◽  
Juan P. Bolan˜os ◽  
John M. Land ◽  
John B. Clark
Keyword(s):  
Nitric Oxide ◽  
Mitochondrial Complex ◽  
Complex Iv

scholarly journals Development of pheochromocytoma in ceramide synthase 2 null mice

2015 ◽  
Vol 22 (4) ◽  
pp. 623-632 ◽  
Author(s):  
Woo-Jae Park ◽  
Ori Brenner ◽  
Aviram Kogot-Levin ◽  
Ann Saada ◽  
Alfred H Merrill ◽  
...  
Keyword(s):  
Acyl Chain ◽  
Null Mouse ◽  
Ceramide Synthase ◽  
Complex Iv ◽  
Acyl Chain Length ◽  
Disease Associated Genes ◽  
Length Analysis ◽  
The Brain ◽  
Reduced Activity

Pheochromocytoma (PCC) and paraganglioma are rare neuroendocrine tumors of the adrenal medulla and sympathetic and parasympathetic paraganglia, for which mutations in ∼15 disease-associated genes have been identified. We now document the role of an additional gene in mice, the ceramide synthase 2 (CerS2) gene. CerS2, one of six mammalian CerS, synthesizes ceramides with very-long (C22–C24) chains. The CerS2 null mouse has been well characterized and displays lesions in several organs including the liver, lung and the brain. We now demonstrate that changes in the sphingolipid acyl chain profile of the adrenal gland lead to the generation of adrenal medullary tumors. Histological analyses revealed that about half of the CerS2 null mice developed PCC by ∼13 months, and the rest showed signs of medullary hyperplasia. Norepinephrine and normetanephrine levels in the urine were elevated at 7 months of age consistent with the morphological abnormalities found at later ages. Accumulation of ceroid in the X-zone was observed as early as 2 months of age and as a consequence, older mice displayed elevated levels of lysosomal cathepsins, reduced proteasome activity and reduced activity of mitochondrial complex IV by 6 months of age. Together, these findings implicate an additional pathway that can lead to PCC formation, which involves alterations in the sphingolipid acyl chain length. Analysis of the role of sphingolipids in PCC may lead to further understanding of the mechanism by which PCC develops, and might implicate the sphingolipid pathway as a possible novel therapeutic target for this rare tumor.

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