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Related Concept Videos

Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

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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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Animal Mitochondrial Genetics02:59

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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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Reporter Genes02:11

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Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
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Translocation of Proteins into the Mitochondria01:19

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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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Energy to Drive Translocation01:37

Energy to Drive Translocation

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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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In-vitro Mutagenesis01:16

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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Author Spotlight: Advancing Techniques and Discoveries in Protein Synthesis and Assembly Through Innovative Mitochondrial Research
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Manipulating and elucidating mitochondrial gene expression with engineered proteins.

Christopher P Wallis1,2, Louis H Scott1,2, Aleksandra Filipovska1,2,3

  • 1Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|December 3, 2019
PubMed
Summary

New synthetic biology tools enable manipulation of mitochondrial DNA and RNA, overcoming limitations of conventional genome engineering for studying mitochondrial genetics and disease. These methods offer potential therapeutic applications.

Keywords:
mitochondriamitochondrial diseasemitochondrial restriction enzymesmitochondrial transcription activator-life effectors nucleasesmitochondrial zinc finger nucleasessynthetic biology

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Area of Science:

  • Mitochondrial genetics and molecular biology
  • Synthetic biology applications in cellular engineering

Background:

  • Conventional genome engineering tools are unsuitable for studying the unique mitochondrial genome.
  • Mitochondrial DNA and RNA research is crucial for understanding cellular function and disease.

Purpose of the Study:

  • To review novel synthetic biology-based approaches for modifying mammalian mitochondrial DNA and RNA.
  • To highlight the potential of these tools for mitochondrial research and therapeutics.

Main Methods:

  • Review of transcription activator-like effector nucleases (TALENs) for mitochondrial genome editing.
  • Discussion of zinc finger nucleases (ZFNs) in mitochondrial DNA and RNA manipulation.
  • Exploration of engineered RNA-binding proteins for targeted mitochondrial RNA modification.

Main Results:

  • Synthetic biology tools offer unprecedented control over mitochondrial DNA and RNA levels.
  • These methods facilitate the study of mitochondrial genotype-phenotype relationships.
  • Demonstration of techniques to manipulate and visualize mitochondrial processes.

Conclusions:

  • Newly developed synthetic biology tools overcome previous limitations in mitochondrial genome engineering.
  • These approaches are vital for advancing the study of mitochondrial genetics.
  • Engineered nucleases and RNA-binding proteins show promise for future mitochondrial therapeutics.