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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Phosphatidylethanolamine enhances amyloid fiber-dependent membrane fragmentation
Michele F M Sciacca1, Jeffrey R Brender, Dong-Kuk Lee
1Departments of Biophysics and Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, United States.
Biochemistry
|September 14, 2012
Summary
Phosphatidylethanolamine (PE) lipids influence amyloid toxicity by modulating how islet amyloid polypeptide (IAPP) interacts with cell membranes. PE lipids can hinder early IAPP binding but enhance membrane damage as IAPP fibers grow.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Amyloid-forming peptides are linked to cellular toxicity through cell membrane disruption.
- In vitro studies using model membranes are crucial but require accurate cell membrane mimicry.
- The role of specific membrane lipid compositions in amyloid toxicity remains underexplored.
Purpose of the Study:
- To investigate how membrane composition, specifically phosphatidylethanolamine (PE) lipids, affects the membrane disruptive potential of islet amyloid polypeptide (IAPP).
- To elucidate the mechanism by which PE lipids modulate IAPP-induced membrane damage.
Main Methods:
- Combined measurements of membrane binding, membrane permeabilization, and amyloid fiber formation.
- Utilized model membrane systems to study IAPP interactions.
Main Results:
- Phosphatidylethanolamine (PE) headgroups significantly modulate IAPP-induced membrane disruption.
- PE lipids were found to inhibit the interaction of prefibrillar IAPP with membranes.
- PE lipids enhanced membrane disruption associated with IAPP fiber growth on the membrane surface, acting via a detergent-like mechanism.
Conclusions:
- Membrane composition, particularly the presence of PE lipids, plays a critical role in determining the toxicity of amyloidogenic proteins like IAPP.
- PE lipids exhibit a dual role, hindering initial IAPP interaction but promoting membrane damage during fiber formation.
- These findings offer insights into the mechanisms of amyloid-mediated membrane disruption and suggest potential roles for PE lipids in pathologies involving amyloid aggregation.
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