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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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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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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
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Labelling and Visualization of Mitochondrial Genome Expression Products in Baker's Yeast Saccharomyces cerevisiae
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Allotopic expression of mitochondrial genes: Basic strategy and progress.

I Made Artika1,2

  • 1Department of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Darmaga Campus, Bogor 16680, Indonesia.

Genes & Diseases
|December 18, 2020
PubMed
Summary

Allotopic expression relocates mitochondrial genes to the nucleus for therapeutic potential in mitochondrial diseases. This strategy shows promise, with one therapy entering clinical trials, but requires further optimization.

Keywords:
Allotopic expressionGene therapyMitochondriaMitochondrial geneProtein targeting

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Mitochondrial genes encode essential proteins but are encoded on a separate genome.
  • Mitochondrial genetic disorders arise from mutations in these genes.
  • Allotopic expression offers a strategy to address these genetic defects.

Purpose of the Study:

  • To review the strategy of allotopic expression for mitochondrial genes.
  • To discuss its applications in research and therapy.
  • To highlight current progress, challenges, and future prospects.

Main Methods:

  • Recoding mitochondrial genes for nuclear expression.
  • Ensuring proper protein translation and targeting to mitochondria.
  • Utilizing model organisms like yeast and human cell lines.

Main Results:

  • Successful nuclear expression and mitochondrial import of several mitochondrial genes in yeast and human cells.
  • Development of allotopic expression as a therapeutic strategy for mitochondrial diseases.
  • Advancement of a Leber's hereditary optic neuropathy (LHON) therapy into phase III clinical trials.

Conclusions:

  • Allotopic expression is a viable strategy for studying and potentially treating mitochondrial disorders.
  • Overcoming challenges in gene expression, protein import, and functional integration is crucial.
  • Continued research holds promise for broader therapeutic applications.