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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

3.0K
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,...
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Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

4.2K
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...
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Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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

Protein Transport into the Inner Mitochondrial Membrane

3.6K
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...
3.6K
Energy to Drive Translocation01:37

Energy to Drive Translocation

2.0K
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...
2.0K
Structure of Porins01:21

Structure of Porins

2.9K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
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Related Experiment Video

Updated: Jun 3, 2025

Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia
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Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia

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Polyproline-Polyornithine Diblock Copolymers with Inherent Mitochondria Tropism.

Camilla Pegoraro1, Ekaterina Karpova2, Yusuf Qutbuddin3

  • 1Príncipe Felipe Research Center, Polymer Therapeutics Lab., Valencia, 46012, Spain.

Advanced Materials (Deerfield Beach, Fla.)
|January 11, 2025
PubMed
Summary

New polypeptide nanocarriers efficiently target mitochondria by recognizing cardiolipin. These cell-penetrating diblock copolymers offer a simple synthesis and potential for safe, effective mitochondrial drug delivery.

Keywords:
cardiolipin‐specific mitochondrial targetingdesign of experiments (doe)membrane remodelingmitochondrial tropismpolypeptide‐based nanoconjugatespolyproline, subcellular organelle targeting

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Last Updated: Jun 3, 2025

Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia
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An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
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An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

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Area of Science:

  • Biomaterials Science
  • Nanomedicine
  • Mitochondrial Biology

Background:

  • Mitochondrial dysfunction is linked to various diseases, necessitating advanced nanomedicines for targeted delivery.
  • Current nanomedicines face challenges with biological barrier penetration, inefficient delivery, and complex synthesis.
  • Mitochondria-specific targeting is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To synthesize and characterize polypeptide-based cell-penetrating diblock copolymers (poly-L-ornithine-polyproline) as mitochondria-targeting nanocarriers.
  • To investigate the mechanisms of cellular uptake, mitochondrial targeting, and therapeutic activity of these nanocarriers.
  • To evaluate the safety and efficacy of the diblock copolymers, particularly in a conjugate form.

Main Methods:

  • Synthesis of poly-L-ornithine (PLO) and polyproline (PLP) diblock copolymers (PLOn-PLPm) using N-carboxyanhydride ring-opening polymerization.
  • Scale-up optimization using a "design of experiments" approach.
  • Investigation of cellular uptake, mitochondrial targeting via cardiolipin (CL) recognition, and anti-tumorigenic activity through physical and biological assays.

Main Results:

  • The diblock copolymers demonstrate rapid, energy-independent cell entry and specific mitochondrial targeting through cardiolipin recognition.
  • Uptake and targetability remain unaffected by stimuli-driven conditions or changes in mitochondrial polarization.
  • The diblock copolymers exhibit inherent, concentration-dependent anti-tumorigenic activity and improved safety profiles in conjugate form.

Conclusions:

  • Polypeptide diblock copolymers offer a simple, scalable method for creating effective mitochondria-targeting nanocarriers.
  • Cardiolipin recognition facilitates efficient mitochondrial accumulation and cellular delivery.
  • These nanocarriers show promise for developing safer and more efficient mitochondrial-targeted therapeutics.