Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction

Motori, E., Atanassov, I., Kochan, S. M. V., Folz-Donahue, K., Sakthivelu, V., Giavalisco, P., et al. (2020). Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction. Sci Adv, 6(35), eaba8271. doi:10.1126/sciadv.aba8271.

Item is

Basisdaten

einblenden: ausblenden:
Genre: Zeitschriftenartikel

Externe Referenzen

einblenden:
ausblenden:
externe Referenz:
https://www.ncbi.nlm.nih.gov/pubmed/32923630 (beliebiger Volltext)
Beschreibung:
-
OA-Status:
Keine Angabe

Urheber

einblenden:
ausblenden:
 Urheber:
Motori, E.1, Autor           
Atanassov, Ilian2, Autor           
Kochan, S. M. V., Autor
Folz-Donahue, K.3, Autor           
Sakthivelu, V., Autor
Giavalisco, P.4, Autor           
Toni, N., Autor
Puyal, J., Autor
Larsson, N.G.1, Autor           
Affiliations:
1Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942286              
2Proteomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942305              
3FACS & Imaging, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942304              
4Metabolomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394018              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: Neurodegeneration in mitochondrial disorders is considered irreversible because of limited metabolic plasticity in neurons, yet the cell-autonomous implications of mitochondrial dysfunction for neuronal metabolism in vivo are poorly understood. Here, we profiled the cell-specific proteome of Purkinje neurons undergoing progressive OXPHOS deficiency caused by disrupted mitochondrial fusion dynamics. We found that mitochondrial dysfunction triggers a profound rewiring of the proteomic landscape, culminating in the sequential activation of precise metabolic programs preceding cell death. Unexpectedly, we identified a marked induction of pyruvate carboxylase (PCx) and other anaplerotic enzymes involved in replenishing tricarboxylic acid cycle intermediates. Suppression of PCx aggravated oxidative stress and neurodegeneration, showing that anaplerosis is protective in OXPHOS-deficient neurons. Restoration of mitochondrial fusion in end-stage degenerating neurons fully reversed these metabolic hallmarks, thereby preventing cell death. Our findings identify a previously unappreciated pathway conferring resilience to mitochondrial dysfunction and show that neurodegeneration can be reversed even at advanced disease stages.

Details

einblenden:
ausblenden:
Sprache(n):
 Datum: 2020-082020-09-15
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: Anderer: 32923630
DOI: 10.1126/sciadv.aba8271
ISSN: 2375-2548 (Electronic)2375-2548 (Linking)
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Sci Adv
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 6 (35) Artikelnummer: - Start- / Endseite: eaba8271 Identifikator: -