Ribosomal transcription is regulated by PGC-1alpha and disturbed in Huntington’s disease

PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. He...

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Veröffentlicht in:Scientific reports 2017-08, Vol.7 (1), p.8513-10, Article 8513
Hauptverfasser: Jesse, Sarah, Bayer, Hanna, Alupei, Marius C., Zügel, Martina, Mulaw, Medhanie, Tuorto, Francesca, Malmsheimer, Silke, Singh, Karmveer, Steinacker, Jürgen, Schumann, Uwe, Ludolph, Albert C., Scharffetter-Kochanek, Karin, Witting, Anke, Weydt, Patrick, Iben, Sebastian
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Sprache:eng
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Zusammenfassung:PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1α localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I. Upon activation PGC-1α associates with the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter. This induces RNA polymerase I transcription under different stress conditions in cell culture and mouse models as well as in healthy humans and is impaired already in early stages of human Huntington’s disease. This novel molecular link between ribosomal and mitochondrial biogenesis helps to explain sarcopenia and cachexia in diseases of neurodegenerative origin.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-09148-7