Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A VDAC1-Derived N-Terminal Peptide Inhibits Mutant SOD1-VDAC1 Interactions and Toxicity in the SOD1 Model of ALS
Ben Gurion Univ Negev, Dept Life Sci, Natl Inst Biotechnol Negev, Beer Sheva, Israel.
Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel.
Ben Gurion Univ Negev, Dept Life Sci, Natl Inst Biotechnol Negev, Beer Sheva, Israel.
Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel.
Show others and affiliations
2019 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 13, article id 346Article in journal (Refereed) Published
Abstract [en]

Mutations in superoxide dismutase (SOD1) are the second most common cause of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease caused by the death of motor neurons in the brain and spinal cord. SOD1 neurotoxicity has been attributed to aberrant accumulation of misfolded SOD1, which in its soluble form binds to intracellular organelles, such as mitochondria and ER, disrupting their functions. Here, we demonstrate that mutant SOD1 binds specifically to the N-terminal domain of the voltage-dependent anion channel (VDAC1), an outer mitochondrial membrane protein controlling cell energy, metabolic and survival pathways. Mutant SOD1(G93A) and SOD1(G85R), but not wild type SOD1, directly interact with VDAC1 and reduce its channel conductance. No such interaction with N-terminal-truncated VDAC1 occurs. Moreover, a VDAC1-derived N-terminal peptide inhibited mutant SOD1-induced toxicity. Incubation of motor neuron-like NSC-34 cells expressing mutant SOD1 or mouse embryonic stem cell-derived motor neurons with different VDAC1 N-terminal peptides resulted in enhanced cell survival. Taken together, our results establish a direct link between mutant SOD1 toxicity and the VDAC1 N-terminal domain and suggest that VDAC1 N-terminal peptides targeting mutant SOD1 provide potential new therapeutic strategies for ALS.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 13, article id 346
Keywords [en]
ALS, misfolded SOD1, mutant SOD1, N-terminal peptide, VDAC1
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-393659DOI: 10.3389/fncel.2019.00346ISI: 000480746900001OAI: oai:DiVA.org:uu-393659DiVA, id: diva2:1354551
Available from: 2019-09-25 Created: 2019-09-25 Last updated: 2019-09-25Bibliographically approved

Open Access in DiVA

fulltext(4630 kB)33 downloads
File information
File name FULLTEXT01.pdfFile size 4630 kBChecksum SHA-512
450921cf4d3da2080376b0bbeab03f6608335c1b2615f0526492d7b36ff32df0bdf0009be9ac4db7f0c576520d9c1859e8be20dc077cb50dc453cebd65e7ff76
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Hoeber, JanKozlova, Elena N.
By organisation
Department of Neuroscience
In the same journal
Frontiers in Cellular Neuroscience
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 33 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 42 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf