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A VDAC1-Derived N-T...
A VDAC1-Derived N-Terminal Peptide Inhibits Mutant SOD1-VDAC1 Interactions and Toxicity in the SOD1 Model of ALS
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- Shteinfer-Kuzmine, Anna (author)
- Ben Gurion Univ Negev, Dept Life Sci, Natl Inst Biotechnol Negev, Beer Sheva, Israel
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- Argueti, Shirel (author)
- Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel
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- Gupta, Rajeev (author)
- Ben Gurion Univ Negev, Dept Life Sci, Natl Inst Biotechnol Negev, Beer Sheva, Israel
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- Shvil, Neta (author)
- Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel
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- Abu-Hamad, Salah (author)
- Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel
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- Gropper, Yael (author)
- Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel
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- Hoeber, Jan, 1986- (author)
- Uppsala universitet,Institutionen för neurovetenskap
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- Magri, Andrea (author)
- Univ Catania, Dept Biol Geol & Environm Sci, Catania, Italy
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- Messina, Angela (author)
- Univ Catania, Dept Biol Geol & Environm Sci, Catania, Italy
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- Kozlova, Elena N. (author)
- Uppsala universitet,Institutionen för neurovetenskap
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- Shoshan-Barmatz, Varda (author)
- Ben Gurion Univ Negev, Dept Life Sci, Natl Inst Biotechnol Negev, Beer Sheva, Israel
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- Israelson, Adrian (author)
- Ben Gurion Univ Negev, Dept Physiol & Cell Biol, Fac Hlth Sci, Zlotowski Ctr Neurosci, Beer Sheva, Israel
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(creator_code:org_t)
- 2019-08-14
- 2019
- English.
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In: Frontiers in Cellular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5102. ; 13
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- ALS
- misfolded SOD1
- mutant SOD1
- N-terminal peptide
- VDAC1
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Shteinfer-Kuzmin ...
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Argueti, Shirel
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Gupta, Rajeev
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Shvil, Neta
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Abu-Hamad, Salah
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Gropper, Yael
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show more...
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Hoeber, Jan, 198 ...
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Magri, Andrea
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Messina, Angela
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Kozlova, Elena N ...
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Shoshan-Barmatz, ...
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Israelson, Adria ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Frontiers in Cel ...
- By the university
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Uppsala University