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Cytosolic Trapping ...
Cytosolic Trapping of a Mitochondrial Heat Shock Protein Is an Early Pathological Event in Synucleinopathies
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- Szegő, Éva M. (författare)
- University Medical Center Göttingen
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- Dominguez-Meijide, Antonio (författare)
- University Medical Center Göttingen
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- Gerhardt, Ellen (författare)
- University Medical Center Göttingen
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- König, Annekatrin (författare)
- University Medical Center Göttingen
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- Koss, David J. (författare)
- University of Newcastle upon Tyne
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- Li, Wen (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang
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- Pinho, Raquel (författare)
- University Medical Center Göttingen
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- Fahlbusch, Christiane (författare)
- University Medical Center Göttingen
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- Johnson, Mary (författare)
- University of Newcastle upon Tyne
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- Santos, Patricia (författare)
- University Medical Center Göttingen
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- Villar-Piqué, Anna (författare)
- University Medical Center Göttingen
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- Thom, Tobias (författare)
- University Medical Center Göttingen,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Rizzoli, Silvio (författare)
- University Medical Center Göttingen
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- Schmitz, Matthias (författare)
- University Medical Center Göttingen,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Li, Jiayi (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang
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- Zerr, Inga (författare)
- German Center for Neurodegenerative Diseases (DZNE), Bonn,University Medical Center Göttingen
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- Attems, Johannes (författare)
- University of Newcastle upon Tyne
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- Jahn, Olaf (författare)
- Max Planck Institute of Experimental Medicine
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- Outeiro, Tiago F. (författare)
- University Medical Center Göttingen,Max Planck Institute of Experimental Medicine,University of Newcastle upon Tyne
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska.
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:1, s. 6-77
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Alpha-synuclein (aSyn) accumulates in intracellular inclusions in synucleinopathies, but the molecular mechanisms leading to disease are unclear. We identify the 10 kDa heat shock protein (HSP10) as a mediator of aSyn-induced mitochondrial impairments in striatal synaptosomes. We find an age-associated increase in the cytosolic levels of HSP10, and a concomitant decrease in the mitochondrial levels, in aSyn transgenic mice. The levels of superoxide dismutase 2, a client of the HSP10/HSP60 folding complex, and synaptosomal spare respiratory capacity are also reduced. Overexpression of HSP10 ameliorates aSyn-associated mitochondrial dysfunction and delays aSyn pathology in vitro and in vivo. Altogether, our data indicate that increased levels of aSyn induce mitochondrial deficits, at least partially, by sequestering HSP10 in the cytosol and preventing it from acting in mitochondria. Importantly, these alterations manifest first at presynaptic terminals. Our study not only provides mechanistic insight into synucleinopathies but opens new avenues for targeting underlying cellular pathologies. Szegő et al. identify HSP10 as a modulator of alpha-synuclein-induced mitochondrial impairment in striatal synaptosomes. Age-associated increase in the cytosolic and decrease in mitochondrial levels of HSP10 results in a reduction in the levels of SOD2 and of synaptosomal ATP production on demand. HSP10 overexpression delays alpha-synuclein pathology both in vitro and in vivo.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- alpha-synuclein
- HSP10
- mitochondria
- Parkinson's disease
- proteostasis
- striatum
- synaptosome
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Szegő, Éva M.
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Dominguez-Meijid ...
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Gerhardt, Ellen
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König, Annekatri ...
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Koss, David J.
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Li, Wen
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visa fler...
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Pinho, Raquel
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Fahlbusch, Chris ...
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Johnson, Mary
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Santos, Patricia
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Villar-Piqué, An ...
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Thom, Tobias
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Rizzoli, Silvio
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Schmitz, Matthia ...
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Li, Jiayi
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Zerr, Inga
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Attems, Johannes
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Jahn, Olaf
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Outeiro, Tiago F ...
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