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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

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.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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.
Most of the mitochondrial precursors...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

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.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Energy to Drive Translocation01:37

Energy to Drive Translocation

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.
Generally, polypeptides are unfolded by two distinct...

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Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube (SWCNT)-delivered MALAT1 Antisense Oligos
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Peptide-based carbon nanotubes for mitochondrial targeting.

Alessia Battigelli1, Julie Russier, Enrica Venturelli

  • 1Department of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, Trieste, 34127, Italy. prato@units.it.

Nanoscale
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Summary

Researchers developed peptide-based multi-walled carbon nanotubes (MWCNTs) to target mitochondria. This innovation could lead to new therapies for mitochondrial DNA diseases by delivering therapeutic oligonucleotides.

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Localization and Relative Quantification of Carbon Nanotubes in Cells with Multispectral Imaging Flow Cytometry

Published on: December 12, 2013

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cell Biology

Background:

  • Mitochondrial DNA (mtDNA) mutations cause various genetic diseases.
  • Current therapeutic strategies for mtDNA diseases are limited.
  • Targeting mitochondria is a promising approach for novel treatments.

Purpose of the Study:

  • To design and synthesize peptide-based multi-walled carbon nanotubes (MWCNTs) for targeted mitochondrial delivery.
  • To functionalize MWCNTs with a mitochondrial targeting sequence (MTS) for enhanced cellular uptake.
  • To investigate the potential of MTS-MWCNTs for delivering therapeutic oligonucleotides to mitochondria.

Main Methods:

  • Covalent functionalization of MWCNTs with a synthetic mitochondrial targeting sequence (MTS).
  • Fluorescent labeling of MTS-MWCNT conjugates for visualization.
  • Subcellular localization studies in murine RAW 264.7 macrophages and human HeLa cells using wide-field epifluorescence microscopy, confocal laser scanning microscopy (CLSM), and transmission electron microscopy (TEM).
  • Analysis of isolated organelles using TEM to confirm mitochondrial localization.

Main Results:

  • Successful synthesis and covalent functionalization of MWCNTs with MTS.
  • Demonstrated successful uptake and specific localization of MTS-MWCNT conjugates into the mitochondria of both cell types.
  • Microscopy techniques confirmed the intracellular distribution and mitochondrial targeting of the functionalized MWCNTs.
  • TEM analysis of isolated organelles provided definitive evidence of mitochondrial localization.

Conclusions:

  • Peptide-based MWCNTs functionalized with MTS can effectively target mitochondria.
  • This approach represents a significant step towards developing novel nanocarriers for therapeutic oligonucleotide delivery to mitochondria.
  • The developed MTS-MWCNTs hold promise for future applications in treating mitochondrial DNA-related genetic disorders.