Related Experiment Video

Updated: May 7, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

Mitochondrial permeability transition pore is a potential drug target for neurodegeneration

Valasani Koteswara Rao1, Emily A Carlson1, Shirley Shidu Yan1

  • 1Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66047, USA.

Biochimica Et Biophysica Acta
|September 24, 2013
PubMed

Insights

The mitochondrial permeability transition pore (mPTP), regulated by cyclophilin D, contributes to neuronal injury in Alzheimer's disease (AD). Blocking the interaction between amyloid beta and CypD may offer a therapeutic strategy for AD.

Area of Science:

  • Neuroscience
  • Mitochondrial Biology
  • Neurodegenerative Diseases

Background:

  • The mitochondrial permeability transition pore (mPTP) is implicated in neuronal injury associated with aging and neurodegenerative diseases like Alzheimer's disease (AD).
  • mPTP formation is influenced by reactive oxygen species (ROS) and intracellular calcium, leading to neuronal cell death.
  • Cyclophilin D (CypD) is a key component of the mPTP and plays a role in ischemia/reperfusion injury.

Purpose of the Study:

  • To review recent advancements concerning the mPTP.
  • To explore the mPTP as a potential therapeutic target for neurodegenerative diseases, particularly AD.
  • To highlight the role of CypD in AD pathogenesis.

Main Methods:

  • Review of existing literature on mPTP, CypD, and AD.
  • Analysis of the interaction between amyloid beta peptide (Aβ) and CypD.
  • Examination of the downstream effects of mPTP formation on mitochondrial function and neuronal integrity.

Main Results:

  • The interaction between Aβ and CypD potentiates mPTP formation, leading to mitochondrial dysfunction.
  • Aβ-induced mPTP opening results in decreased mitochondrial membrane potential, impaired respiration, increased oxidative stress, and cytochrome c release.
  • Impaired axonal mitochondrial transport is observed due to Aβ-CypD interaction and subsequent mPTP activation.
  • CypD-dependent mPTP is directly linked to cellular and synaptic perturbations in AD pathogenesis.

Conclusions:

  • The CypD-dependent mPTP is a critical mediator of neuronal injury in Alzheimer's disease.
  • Targeting the Aβ-CypD interaction with small molecules presents a promising therapeutic avenue to mitigate Aβ neurotoxicity.
  • Further research into mPTP modulation could lead to novel treatments for AD and other neurodegenerative conditions.
Keywords:
Alzheimer's diseaseAmyloid βCyclophilin DMitochondrial permeability transition poreNeurodegeneration

More Related Videos

Simultaneous Measurement of Mitochondrial Calcium and Mitochondrial Membrane Potential in Live Cells by Fluorescent Microscopy08:43

Simultaneous Measurement of Mitochondrial Calcium and Mitochondrial Membrane Potential in Live Cells by Fluorescent Microscopy

Published on: January 24, 2017

Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria13:42

Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria

Published on: September 7, 2012

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...
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...
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...
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...