Titlebar

Export bibliographic data
Literature by the same author
plus on the publication server
plus at Google Scholar

 

Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin

DOI zum Zitieren dieses Dokuments: https://doi.org/10.1016/j.celrep.2015.02.009

Title data

Braun, Ralf J. ; Sommer, Cornelia ; Leibiger, Christine ; Gentier, Romina J.G. ; Dumit, Verónica I. ; Paduch, Katrin ; Eisenberg, Tobias ; Habernig, Lukas ; Trausinger, Gert ; Magnes, Christoph ; Pieber, Thomas ; Sinner, Frank ; Dengjel, Jörn ; van Leeuwen, Fred W. ; Kroemer, Guido ; Madeo, Frank:
Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin.
In: Cell Reports. Vol. 10 (2015) Issue 9 . - 1557 - 1571.
ISSN 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2015.02.009

[img] PDF
1-s2.0-S2211124715001370-main.pdf - Published Version
Available under License Creative Commons BY-NC-ND 3.0: Attribution, Noncommercial, No Derivative Works .

Download (4MB)

Project information

Project title:
Project's official titleProject's id
Open Access PublizierenNo information

Abstract

Summary Neuronal accumulation of UBB+1, a frameshift variant of ubiquitin B, is a hallmark of Alzheimer’s disease (AD). How UBB+1 contributes to neuronal dysfunction remains elusive. Here, we show that in brain regions of {AD} patients with neurofibrillary tangles UBB+1 co-exists with VMS1, the mitochondrion-specific component of the ubiquitin-proteasome system (UPS). Expression of UBB+1 in yeast disturbs the UPS, leading to mitochondrial stress and apoptosis. Inhibiting {UPS} activity exacerbates while stimulating {UPS} by the transcription activator Rpn4 reduces UBB+1-triggered cytotoxicity. High levels of the Rpn4 target protein Cdc48 and its cofactor Vms1 are sufficient to relieve programmed cell death. We identified the UBB+1-induced enhancement of the basic amino acids arginine, ornithine, and lysine at mitochondria as a decisive toxic event, which can be reversed by Cdc48/Vms1-mediated proteolysis. The fact that AD-induced cellular dysfunctions can be avoided by {UPS} activity at mitochondria has potentially far-reaching pathophysiological implications.

Further data

Item Type: Article in a journal
DDC Subjects: 500 Science > 570 Life sciences, biology
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Professorship Cell Biology
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology
Language: English
Originates at UBT: Yes
Date Deposited: 08 Feb 2017 10:44
Last Modified: 13 Feb 2017 10:28
URI: https://epub.uni-bayreuth.de/id/eprint/3124

Downloads

Downloads per month over past year