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Related Concept Videos

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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Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

4.4K
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...
4.4K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

3.2K
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,...
3.2K
Amyloid Fibrils03:03

Amyloid Fibrils

9.7K
Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
9.7K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

4.0K
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...
4.0K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

3.2K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.2K

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Related Experiment Video

Updated: Aug 19, 2025

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

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Amyloid precursor protein and mitochondria.

Taylor A Strope1, Heather M Wilkins2

  • 1University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: https://twitter.com/OneDayDrTay.

Current Opinion in Neurobiology
|December 3, 2022
PubMed
Summary

Alzheimer's disease (AD) research shows amyloid precursor protein (APP) and its processing enzymes in mitochondria. This mitochondrial localization impacts cellular energy production and AD pathology.

Keywords:
Alzheimer's diseaseAmyloid precursor proteinBioenergeticsMitochondriaγ-secretase

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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is hallmarked by amyloid precursor protein (APP) to amyloid beta (Aβ) processing.
  • The amyloid cascade hypothesis for AD pathogenesis faces challenges due to recent therapeutic failures.
  • Metabolic deficits and mitochondrial dysfunction are consistently observed in AD patients.

Purpose of the Study:

  • To review evidence for APP and γ-secretase localization within mitochondria.
  • To discuss the functional implications of APP processing in the mitochondrial compartment.
  • To explore the role of APP and its metabolites in regulating mitochondrial function.

Main Methods:

  • Literature review of studies investigating APP and γ-secretase localization.
  • Analysis of research on mitochondrial APP processing.
  • Examination of the impact of APP cleavage products on mitochondrial bioenergetics.

Main Results:

  • Evidence supports the presence and activity of APP and γ-secretase within mitochondria.
  • Mitochondrial localization of APP affects mitochondrial function.
  • APP processing within mitochondria has implications for AD pathogenesis.

Conclusions:

  • APP and γ-secretase's presence in mitochondria is significant for AD pathology.
  • Mitochondrial APP processing represents a potential therapeutic target for Alzheimer's disease.
  • Further research into mitochondrial APP metabolism is warranted for AD treatment strategies.