Alpha-synuclein oligomers distinctively permeabilize model plasma and mitochondrial membranes

A.N.D. Stefanovic, M.T. Stöckl, M.M.A.E. Claessens, V. Subramaniam

Research output: Contribution to journalMeeting AbstractOther research output

Abstract

Alpha-synuclein (aS) oligomers are increasingly considered to be responsible for the death of dopaminergic neurons in Parkinson’s disease (PD). The toxicity mechanism of aS oligomers likely involves membrane permeabilization. Even though it is well-established that aS oligomers bind and permeabilize vesicles composed of negatively charged lipids, little attention has been given to the interaction of oligomers with bilayers of physiologically relevant lipid compositions. We demonstrate that aS binds to bilayers composed of lipid mixtures that mimic those of plasma and mitochondrial membranes. Circular dichroism experiments indicate that binding induces conformational changes in both oligomeric and monomeric aS. The membrane leakage that results from oligomer binding to physiologically relevant membranes differs from that observed for simple artificial model bilayers. Instead of inducing fast content release, oligomer binding increases the permeability of artificial mitochondrial membranes resulting in a slow loss of content. Oligomers are not able to induce leakage in artificial plasma membranes even after long-term incubation. The results uggest that the mitochondrial membrane is the
Original languageEnglish
Article numberP-464
Pages (from-to)S156-S156
JournalEuropean biophysics journal
Volume42
Issue numberSuppl. 1
DOIs
Publication statusPublished - 2013
Event9th European Biophysics Congress, EBSA 2013 - Lisbon, Portugal
Duration: 13 Jul 201317 Jul 2013
Conference number: 9

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alpha-Synuclein
Mitochondrial Membranes
Cell Membrane
Artificial Membranes
Membranes
Lipids
Dopaminergic Neurons
Lipid Bilayers
Circular Dichroism
Parkinson Disease
Permeability

Cite this

Stefanovic, A.N.D. ; Stöckl, M.T. ; Claessens, M.M.A.E. ; Subramaniam, V. / Alpha-synuclein oligomers distinctively permeabilize model plasma and mitochondrial membranes. In: European biophysics journal. 2013 ; Vol. 42, No. Suppl. 1. pp. S156-S156.
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Alpha-synuclein oligomers distinctively permeabilize model plasma and mitochondrial membranes. / Stefanovic, A.N.D.; Stöckl, M.T.; Claessens, M.M.A.E.; Subramaniam, V.

In: European biophysics journal, Vol. 42, No. Suppl. 1, P-464, 2013, p. S156-S156.

Research output: Contribution to journalMeeting AbstractOther research output

TY - JOUR

T1 - Alpha-synuclein oligomers distinctively permeabilize model plasma and mitochondrial membranes

AU - Stefanovic, A.N.D.

AU - Stöckl, M.T.

AU - Claessens, M.M.A.E.

AU - Subramaniam, V.

N1 - Special issue: 9th EBSA European Biophysics Congress, 13-17 July 2013, Lisbon, Portugal - Abstracts

PY - 2013

Y1 - 2013

N2 - Alpha-synuclein (aS) oligomers are increasingly considered to be responsible for the death of dopaminergic neurons in Parkinson’s disease (PD). The toxicity mechanism of aS oligomers likely involves membrane permeabilization. Even though it is well-established that aS oligomers bind and permeabilize vesicles composed of negatively charged lipids, little attention has been given to the interaction of oligomers with bilayers of physiologically relevant lipid compositions. We demonstrate that aS binds to bilayers composed of lipid mixtures that mimic those of plasma and mitochondrial membranes. Circular dichroism experiments indicate that binding induces conformational changes in both oligomeric and monomeric aS. The membrane leakage that results from oligomer binding to physiologically relevant membranes differs from that observed for simple artificial model bilayers. Instead of inducing fast content release, oligomer binding increases the permeability of artificial mitochondrial membranes resulting in a slow loss of content. Oligomers are not able to induce leakage in artificial plasma membranes even after long-term incubation. The results uggest that the mitochondrial membrane is the

AB - Alpha-synuclein (aS) oligomers are increasingly considered to be responsible for the death of dopaminergic neurons in Parkinson’s disease (PD). The toxicity mechanism of aS oligomers likely involves membrane permeabilization. Even though it is well-established that aS oligomers bind and permeabilize vesicles composed of negatively charged lipids, little attention has been given to the interaction of oligomers with bilayers of physiologically relevant lipid compositions. We demonstrate that aS binds to bilayers composed of lipid mixtures that mimic those of plasma and mitochondrial membranes. Circular dichroism experiments indicate that binding induces conformational changes in both oligomeric and monomeric aS. The membrane leakage that results from oligomer binding to physiologically relevant membranes differs from that observed for simple artificial model bilayers. Instead of inducing fast content release, oligomer binding increases the permeability of artificial mitochondrial membranes resulting in a slow loss of content. Oligomers are not able to induce leakage in artificial plasma membranes even after long-term incubation. The results uggest that the mitochondrial membrane is the

U2 - 10.1007/s00249-013-0917-x

DO - 10.1007/s00249-013-0917-x

M3 - Meeting Abstract

VL - 42

SP - S156-S156

JO - European biophysics journal

JF - European biophysics journal

SN - 0175-7571

IS - Suppl. 1

M1 - P-464

ER -