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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.
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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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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Drug Delivery: Overview01:16

Drug Delivery: Overview

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The selection of a drug's delivery route depends upon its physicochemical properties, including lipid or water solubility and ionization, as well as the therapeutic requirement, such as immediate or sustained effect. These routes can be divided into three primary categories: enteral, parenteral, and topical.
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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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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.
Sorting of outer membrane proteins:
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Drug Delivery: Miscellaneous Routes01:22

Drug Delivery: Miscellaneous Routes

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Drug delivery methods like oral inhalation, nasal sprays, transdermal patches, eye drops, intravitreal injection,  and rectal administration provide localized effects with reduced toxicity.
Oral inhalation and nasal sprays swiftly transfer drugs across the respiratory epithelium's mucosal layer. Inhaled glucocorticoids and bronchodilators directly target lung conditions such as asthma, while fluticasone nasal spray mitigates allergic rhinitis.
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Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
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Drug delivery systems for mitochondrial targeting.

Sofia Tagliavini1,2, Mara Filippini1, Alessandro Anderlini1,2

  • 1NanotechLab, TeFarTI, Department Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy. ilaria.ottonelli@unimore.it.

Nanoscale
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Summary
This summary is machine-generated.

Targeting mitochondria with nanoparticles offers a promising strategy for treating mitochondrial diseases and cancer. These advanced nanomedicines enable precise delivery of therapeutics to restore organelle function and induce tumor cell death.

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Area of Science:

  • Cell Biology
  • Nanomedicine
  • Therapeutics

Background:

  • Mitochondria are vital organelles implicated in numerous physiological and pathological processes.
  • Mitochondrial dysfunction, stemming from genetic mutations or other factors, underlies a wide range of mitochondrial diseases.
  • Targeting mitochondria is crucial for treating conditions like oxidative stress disorders, neurological diseases, and for anticancer therapies.

Purpose of the Study:

  • To review recent advancements in nanosystem-based approaches for mitochondria-targeted delivery.
  • To explore the potential of nanoparticles for delivering nucleic acid therapeutics and small molecule drugs to mitochondria.
  • To highlight the promise of rationally designed nanomedicines for subcellular-level therapeutic delivery.

Main Methods:

  • Review of recent scientific literature on mitochondria-targeted delivery systems.
  • Focus on nanoparticle-based strategies utilizing specific ligands for mitochondrial targeting.
  • Examination of the delivery of nucleic acids (DNA, RNA) and small molecule drugs.

Main Results:

  • Nanoparticles functionalized with specific ligands represent a promising strategy to overcome biological barriers, including the mitochondrial membrane.
  • Nanosystem-based approaches enable targeted delivery of various therapeutic agents to mitochondria.
  • Rationally designed nanomedicines demonstrate significant potential for precise subcellular therapeutic interventions.

Conclusions:

  • Targeted delivery systems are essential for restoring mitochondrial function and treating mitochondrial diseases.
  • Nanoparticle-based strategies offer a viable approach to overcome mitochondrial barriers for therapeutic delivery.
  • Mitochondria-targeted nanomedicines hold significant promise for precise therapeutic applications at the subcellular level.