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Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

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Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
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Phase II Reactions: Methylation Reactions01:17

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Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
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Export of Mitochondrial and Chloroplast Genes02:19

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A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
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Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes02:16

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The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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A method involving the transformation of methyl ketones to carboxylic acids using excess base and halogen is called the haloform reaction. It begins with the deprotonation of α hydrogen to form an enolate ion which reacts with the electrophilic halogen to give an α-halo ketone. The step continues until all the α protons are substituted to form a trihalomethyl ketone. The resulting molecule is unstable, and in the presence of a hydroxide base, it readily undergoes nucleophilic...
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Methodology for Accurate Detection of Mitochondrial DNA Methylation
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Reduced nuclear DNA methylation and mitochondrial transcript changes in adenomas do not associate with mtDNA

M J Morris1, L B Hesson2, R C Poulos2,3

  • 11Department of Pharmacology, School of Medical Sciences, UNSW Sydney, Sydney, NSW Australia.

Biomarker Research
|January 9, 2019
PubMed
Summary

Mitochondrial DNA (mtDNA) methylation is low in colorectal cancer (CRC) and does not correlate with gene transcription changes. Therefore, mtDNA methylation is unlikely to serve as an early biomarker for CRC.

Keywords:
AdenomaColorectal cancerDNA methylationMitochondriamtDNA

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Area of Science:

  • Genomics
  • Cancer Biology
  • Mitochondrial Biology

Background:

  • Colorectal cancer (CRC) is characterized by altered mitochondrial function and nuclear DNA methylation.
  • The role and occurrence of DNA methylation in the mitochondrial genome (mtDNA) within CRC remain unclear and controversial.
  • Mitochondria contain a vital 16 kb circular genome essential for their function.

Purpose of the Study:

  • To investigate the link between mitochondrial DNA methylation and mitochondrial gene transcription in colorectal adenomas.
  • To evaluate the potential of mitochondrial DNA methylation as a biomarker for early-stage colorectal cancer.

Main Methods:

  • RNA-sequencing and Whole Genome Bisulphite Sequencing (WGBS) were performed on mtDNA-enriched DNA.
  • Samples included normal mucosa and paired adenoma tissues from patients.
  • Analysis focused on transcriptional changes and methylation patterns in both nuclear and mitochondrial genomes.

Main Results:

  • Adenomas exhibited reduced mitochondrial proton transport and decreased expression of three mtDNA-transcribed tRNAs compared to normal mucosa.
  • Overall nuclear DNA methylation decreased in adenomas (68%) versus normal mucosa (75%).
  • Mitochondrial DNA methylation was low (1%) in both normal and adenoma tissues, with methylation clusters found at ribosomal RNA genes, showing no significant difference between tissue types.

Conclusions:

  • Low-level methylation exists at specific sites within the mitochondrial genome.
  • This methylation is not associated with altered mitochondrial gene transcription in adenomas.
  • Given the lack of large-scale changes, mitochondrial DNA methylation is unlikely to be a suitable biomarker for early-stage colorectal cancer.