Faculty Opinions recommendation of A cluster of metabolic defects caused by mutation in a mitochondrial tRNA.

2004 ◽  
Author(s):  
M Flint Beal
Keyword(s):  
Mitochondrial Trna ◽  
Metabolic Defects

scholarly journals Mitochondrial tRNA Mutations Associated With Essential Hypertension: From Molecular Genetics to Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuqi Liu ◽  
Yundai Chen
Keyword(s):  
Essential Hypertension ◽  
Metabolic Disorders ◽  
Atp Synthesis ◽  
Trna Genes ◽  
Mitochondrial Trna ◽  
Mtdna Mutations ◽  
Metabolic Defects ◽  
Trna Structure ◽  
Genetic And Environmental Factors ◽  
High Level

Essential hypertension (EH) is one of the most common cardiovascular diseases worldwide, entailing a high level of morbidity. EH is a multifactorial disease influenced by both genetic and environmental factors, including mitochondrial DNA (mtDNA) genotype. Previous studies identified mtDNA mutations that are associated with maternally inherited hypertension, including tRNAIle m.4263A>G, m.4291T>C, m.4295A>G, tRNAMet m.4435A>G, tRNAAla m.5655A>G, and tRNAMet/tRNAGln m.4401A>G, et al. These mtDNA mutations alter tRNA structure, thereby leading to metabolic disorders. Metabolic defects associated with mitochondrial tRNAs affect protein synthesis, cause oxidative phosphorylation defects, reduced ATP synthesis, and increase production of reactive oxygen species. In this review we discuss known mutations of tRNA genes encoded by mtDNA and the potential mechanisms by which these mutations may contribute to hypertension.

Potential Interventions Against BMPR2-Related Pulmonary Hypertension

2012 ◽  
Vol 11 (1) ◽  
pp. 25-32 ◽  
Author(s):  
James West ◽  
James E. Loyd ◽  
Rizwan Hamid
Keyword(s):  
Therapeutic Interventions ◽  
Great Promise ◽  
Patient Registries ◽  
Metabolic Defects ◽  
Pulmonary Arterial ◽  
Alternative Approaches ◽  
Splicing Defects ◽  
Trafficking Defects ◽  
Molecular Bases ◽  
Near Future

For more than 60 years, researchers have sought to understand the molecular basis of idiopathic pulmonary arterial hypertension (PAH). Recognition of the heritable form of the disease led to the creation of patient registries in the 1980s and 1990s, and discovery of BMPR2 as the cause of roughly 80% of heritable PAH in 2000. With discovery of the disease gene came opportunity for intervention, with focus on 2 alternative approaches. First, it may be possible to correct the effects of BMPR2 mutation directly through interventions targeted at correction of trafficking defects, increasing expression of the unmutated allele, and correction of splicing defects. Second, therapeutic interventions are being targeted at the signaling consequences of BMPR2 mutation. In particular, therapies targeting cytoskeletal and metabolic defects caused by BMPR2 mutation are currently in trials, or will be ready for human trials in the near future. Translation of these findings into therapies is the culmination of decades of research, and holds great promise for treatment of the underlying molecular bases of disease.

X-Linked Hypophosphatemia: Progress in Characterization of Genetic and Metabolic Defects

Nephron ◽  
1989 ◽  
Vol 51 (4) ◽  
pp. 449-453 ◽  
Author(s):  
Gad Kainer ◽  
Edward Spence ◽  
James C.M. Chan
Keyword(s):  
Metabolic Defects

scholarly journals Alterations in Rev-ERBα/BMAL1 ratio and glycated hemoglobin in rotating shift workers: the EuRhythDia study

2021 ◽  
Author(s):  
Stefano Rizza ◽  
Alessio Luzi ◽  
Maria Mavilio ◽  
Marta Ballanti ◽  
Arianna Massimi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Glycated Hemoglobin ◽  
Night Shift ◽  
Multivariate Regression Analysis ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Shift Workers ◽  
Metabolic Defects ◽  
Clock Gene Expression ◽  
Cell Counts

Abstract Objective To detect premature gluco-metabolic defects among night shift workers with disturbances in circadian rhythms. Design and methods We performed a hypothesis-generating, cross-sectional analysis of anthropometric, metabolic, lipid, and inflammation parameters, comparing active (a-NSW, n = 111) and former (f-NSW, n = 98) rotating night shift workers with diurnal workers (controls, n = 69). All participants were hospital nurses. We also evaluated the Pittsburgh Sleep Quality Index (PSQI) and assessed expression of transcription factors REV-ERBα and BMAL1 in peripheral blood mononuclear cells (PBMCs), as indicators of the molecular clock. Results Both a-NSW and f-NSW participants had significantly higher glycated hemoglobin (HbA1c) and white blood cell counts (WBC) (p < 0.001 for both), PSQI global score (p = 0.001) and diastolic blood pressure levels (p = 0.024) compared with controls. Expression of REV-ERBα/BMAL1 RNA in PBMC was significantly higher in a-NSW (p = 0.05) than in f-NSW or control participants. Multivariate regression analysis showed that working status and PSQI were independent determinants of higher HbA1c levels (p < 0.001). Conclusions We demonstrated that young, healthy night shift workers show subclinical abnormalities in HbA1c and changes in peripheral clock gene expression.

scholarly journals Identification of Six Loci in Which Mutations Partially Restore Peroxisome Biogenesis and/or Alleviate the Metabolic Defect of pex2 Mutants in Podospora

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1089-1099
Author(s):  
Gwenaël Ruprich-Robert ◽  
Véronique Berteaux-Lecellier ◽  
Denise Zickler ◽  
Arlette Panvier-Adoutte ◽  
Marguerite Picard
Keyword(s):  
Sole Carbon Source ◽  
Large Scale ◽  
Podospora Anserina ◽  
Developmental Defect ◽  
Dominant Allele ◽  
Peroxisome Biogenesis ◽  
Metabolic Defects ◽  
Metabolic Defect ◽  
Mutant Strains ◽  
Large Scale Screening

Abstract Peroxins (PEX) are proteins required for peroxisome biogenesis. Mutations in PEX genes cause lethal diseases in humans, metabolic defects in yeasts, and developmental disfunctions in plants and filamentous fungi. Here we describe the first large-scale screening for suppressors of a pex mutation. In Podospora anserina, pex2 mutants exhibit a metabolic defect [inability to grow on medium containing oleic acid (OA medium) as sole carbon source] and a developmental defect (inability to differentiate asci in homozygous crosses). Sixty-three mutations able to restore growth of pex2 mutants on OA medium have been analyzed. They fall in six loci (suo1 to suo6) and act as dominant, allele-nonspecific suppressors. Most suo mutations have pleiotropic effects in a pex2+ background: formation of unripe ascospores (all loci except suo5 and suo6), impaired growth on OA medium (all loci except suo4 and suo6), or sexual defects (suo4). Using immunofluorescence and GFP staining, we show that peroxisome biogenesis is partially restored along with a low level of ascus differentiation in pex2 mutant strains carrying either the suo5 or the suo6 mutations. The data are discussed with respect to β-oxidation of fatty acids, peroxisome biogenesis, and cell differentiation.

Sign in / Sign up

Export Citation Format

Share Document