scholarly journals Mitochondrial gene expression in the human gastrointestinal tract

1992 ◽  
Vol 102 (2) ◽  
pp. 307-314
Author(s):  
A.J. Macpherson ◽  
T.P. Mayall ◽  
K.A. Chester ◽  
A. Abbasi ◽  
I. Forgacs ◽  
...  
Keyword(s):  
Small Intestine ◽  
Epithelial Cells ◽  
Respiratory Chain ◽  
Mitochondrial Gene ◽  
In Situ Hybridisation ◽  
Mitochondrial Respiratory Chain ◽  
Basal Cells ◽  
Ribosomal Rnas ◽  
Cell Axis ◽  
Mitochondrial Respiratory

In the human gastrointestinal epithelium, in situ hybridisation demonstrates that 12 S and 16 S mitochondrial ribosomal RNAs show maximal steady-state levels on the surface epithelial cells of the normal small intestine and colon. The mitochondrial mRNAs, cytochrome b and NADH dehydrogenase (IV) have a uniform distribution throughout the crypt and surface (villus) epithelial cells of the small intestine and colon. Histochemical stains for the activity of the mitochondrial respiratory chain enzymes succinate dehydrogenase and cytochrome oxidase also show almost uniform activities throughout the crypt-surface epithelial cell axis in the small and large intestines. In sections of normal human oesophagus the levels of mitochondrial ribosomal RNAs, mitochondrial mRNAs and the activities of mitochondrial respiratory chain enzymes are maximal over the basal cells of the stratified squamous epithelium. These results show a relative increase in mitochondrial ribosomal RNA expression compared with mitochondrial mRNAs in surface cells of simple intestinal epithelia.

scholarly journals Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3’-end processing

2018 ◽  
Author(s):  
Makenzie Saoura ◽  
Christopher A. Powell ◽  
Robert Kopajtich ◽  
Ahmad Alahmad ◽  
Haya H. AL-Balool ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Respiratory Chain ◽  
Mitochondrial Gene ◽  
Mitochondrial Respiratory Chain ◽  
Rna Metabolism ◽  
Mitochondrial Rna ◽  
Functional Link ◽  
Rnase Z ◽  
Mitochondrial Respiratory

AbstractDysfunction of mitochondrial gene expression, caused by mutations in either the mitochondrial or nuclear genomes, is associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA metabolism. For instance, pathogenic mutations have been identified in the genes encoding enzymes involved in the precursor transcript processing, including ELAC2. The ELAC2 gene codes for the mitochondrial RNase Z, which is responsible for endonucleolytic cleavage of the 3’ ends of mitochondrial pre-tRNAs. Here, we report the identification of sixteen novel ELAC2 variants in individuals presenting with mitochondrial respiratory chain deficiency, hypertrophic cardiomyopathy and lactic acidosis. We provided further evidence for the pathogenicity of the three previously reported variants by studying the RNase Z activity in an in vitro system and applied this recombinant system to investigate all novel missense variants, confirming the pathogenic role of these new ELAC2 mutations. We also modelled the residues affected by missense mutation in solved RNase Z structures, providing insight into enzyme structure and function. Finally, we show that primary fibroblasts from the individuals with novel ELAC2 variants have elevated levels of unprocessed mitochondrial RNA precursors. Our study thus broadly confirms the correlation of ELAC2 variants with severe infantile-onset forms of hypertrophic cardiomyopathy and mitochondrial respiratory chain dysfunction. One rare missense variant associated with the occurrence of prostate cancer (p.Arg781His) impairs the mitochondrial RNase Z activity of ELAC2, possibly indicating a functional link between tumorigenesis and mitochondrial RNA metabolism.

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