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Mitochondrial dysfu...
Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response
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- Filograna, Roberta (author)
- Karolinska Institutet,Karolinska Institute
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- Lee, Seungmin (author)
- Karolinska Institute
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- Tiklová, Katarína (author)
- Karolinska Institute
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- Mennuni, Mara (author)
- Karolinska Institutet,Karolinska Institute
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- Jonsson, Viktor, 1987 (author)
- Chalmers University of Technology
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- Ringnér, Markus (author)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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- Gillberg, Linda (author)
- Karolinska Institutet,Karolinska Institute
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- Sopova, Elena (author)
- Karolinska Institutet,Karolinska Institute,Saint Petersburg State University
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- Shupliakov, Oleg (author)
- Karolinska Institutet,Karolinska Institute,Saint Petersburg State University
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- Koolmeister, Camilla (author)
- Karolinska Institutet,Karolinska Institute
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- Olson, L (author)
- Karolinska Institute
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- Perlmann, Thomas (author)
- Karolinska Institutet,Karolinska Institute
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- Larsson, Nils-Göran (author)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2021-09-27
- 2021
- English.
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:9
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Abstract
Subject headings
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- Dopamine (DA) neurons of the midbrain are at risk to become affected by mitochondrial damage over time and mitochondrial defects have been frequently reported in Parkinson's disease (PD) patients. However, the causal contribution of adult-onset mitochondrial dysfunction to PD remains uncertain. Here, we developed a mouse model lacking Mitofusin 2 (MFN2), a key regulator of mitochondrial network homeostasis, in adult midbrain DA neurons. The knockout mice develop severe and progressive DA neuron-specific mitochondrial dysfunction resulting in neurodegeneration and parkinsonism. To gain further insights into pathophysiological events, we performed transcriptomic analyses of isolated DA neurons and found that mitochondrial dysfunction triggers an early onset immune response, which precedes mitochondrial swelling, mtDNA depletion, respiratory chain deficiency and cell death. Our experiments show that the immune response is an early pathological event when mitochondrial dysfunction is induced in adult midbrain DA neurons and that neuronal death may be promoted non-cell autonomously by the cross-talk and activation of surrounding glial cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- By the author/editor
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Filograna, Rober ...
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Lee, Seungmin
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Tiklová, Katarín ...
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Mennuni, Mara
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Jonsson, Viktor, ...
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Ringnér, Markus
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show more...
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Gillberg, Linda
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Sopova, Elena
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Shupliakov, Oleg
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Koolmeister, Cam ...
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Olson, L
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Perlmann, Thomas
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Larsson, Nils-Gö ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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PLoS Genetics
- By the university
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Chalmers University of Technology
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Lund University
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Karolinska Institutet