English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Tau-induced mitochondrial membrane perturbation is dependent upon cardiolipin.

Camilleri, A., Ghio, S., Caruana, M., Weckbecker, D., Schmidt, F., Kamp, F., et al. (2019). Tau-induced mitochondrial membrane perturbation is dependent upon cardiolipin. Biochimica et Biophysica Acta. Biomembranes, (in press). doi:10.1016/j.bbamem.2019.183064.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0004-AF38-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-AF3A-7
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Camilleri, A., Author
Ghio, S., Author
Caruana, M., Author
Weckbecker, D., Author
Schmidt, F., Author
Kamp, F., Author
Leonov, A.1, Author              
Ryazanov, S.1, Author              
Griesinger, C.1, Author              
Giese, A., Author
Cauchi, R. J., Author
Vassallo, N., Author
Affiliations:
1Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              

Content

show
hide
Free keywords: Cardiolipin; Membrane permeabilisation; Mitochondria; Nanopores; Oligomers; Tau
 Abstract: Misfolding and aggregate formation by the tau protein has been closely related with neurotoxicity in a large group of human neurodegenerative disorders, which includes Alzheimer's disease. Here, we investigate the membrane-active properties of tau oligomers on mitochondrial membranes, using minimalist in vitro model systems. Thus, exposure of isolated mitochondria to oligomeric tau evoked a disruption of mitochondrial membrane integrity, as evidenced by a combination of organelle swelling, efflux of cytochrome c and loss of the mitochondrial membrane potential. Tau-induced mitochondrial dysfunction occurred independently of the mitochondrial permeability transition (mPT) pore complex. Notably, mitochondria were rescued by pre-incubation with 10-N-nonyl acridine orange (NAO), a molecule that specifically binds cardiolipin (CL), the signature phospholipid of mitochondrial membranes. Additionally, NAO prevented direct binding of tau oligomers to isolated mitochondria. At the same time, tau proteins exhibited high affinity to CL-enriched membranes, whilst permeabilisation of lipid vesicles also strongly correlated with CL content. Intriguingly, using single-channel electrophysiology, we could demonstrate the formation of non-selective ion-conducting tau nanopores exhibiting multilevel conductances in mito-mimetic bilayers. Taken together, the data presented here advances a scenario in which toxic cytosolic entities of tau protein would target mitochondrial organelles by associating with their CL-rich membrane domains, leading to membrane poration and compromised mitochondrial structural integrity.

Details

show
hide
Language(s): eng - English
 Dates: 2019-09-12
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.bbamem.2019.183064
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Biochimica et Biophysica Acta. Biomembranes
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: - Sequence Number: (in press) Start / End Page: - Identifier: -