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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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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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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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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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Mitochondrial Precursor Proteins01:39

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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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Protein Transport into the Inner Mitochondrial Membrane01:34

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Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
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RNA Delivery to Mitochondria.

Yuma Yamada1,2, Hideyoshi Harashima3

  • 1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. u-ma@pharm.hokudai.ac.jp.

Handbook of Experimental Pharmacology
|April 5, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel mitochondria-targeted drug delivery system (DDS) called MITO-Porter for RNA delivery. This system shows promise for treating mitochondrial diseases through gene therapy, addressing limitations in current treatments.

Keywords:
Gene therapyMITO-PorterMitochondriaMitochondrial drug deliveryRNA deliveryRNA knockdown

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Genetics

Background:

  • The success of mRNA vaccines highlights advances in nucleic acid delivery systems.
  • Mitochondria possess their own genome (mtDNA) and are targets for treating intractable genetic diseases.
  • Current RNA delivery research primarily focuses on the nucleus and cytoplasm, with limited efforts targeting mitochondria.

Purpose of the Study:

  • To provide an overview of mitochondria-targeted gene therapy strategies.
  • To discuss existing studies on mitochondria-targeted RNA delivery.
  • To present the efficacy of a novel mitochondria-targeted drug delivery system (MITO-Porter) for RNA delivery.

Main Methods:

  • Review of current literature on mitochondria-targeted gene therapy and RNA delivery.
  • Development and application of a novel mitochondria-targeted drug delivery system (MITO-Porter).
  • Experimental validation of RNA delivery to mitochondria using the MITO-Porter system.

Main Results:

  • Significant progress in RNA delivery technologies, exemplified by mRNA vaccines.
  • Limited success in developing drug delivery systems (DDS) for mitochondria compared to nuclear/cytoplasmic delivery.
  • Demonstration of successful RNA delivery to mitochondria using the developed MITO-Porter DDS.

Conclusions:

  • Mitochondria-targeted gene therapy holds potential for treating mitochondrial DNA diseases.
  • The MITO-Porter DDS represents a significant advancement in delivering RNA to mitochondria.
  • Further research into mitochondria-targeted RNA delivery is crucial for developing effective gene therapies.