Opis

• Tytuł:
  Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders
• Twórca:
  Aiyar, Raeka S;
  Bohnert, M;
  Duvezin-Caubet, S;
  Voisset, C;
  Gagneur, J;
  Fritsch, ES;
  Couplan, E;
  von der Malsburg, K;
  Funaya, C;
  Soubigou, F;
  Courtin, Courtin F;
  Suresh, Suresh S;
  Kucharczyk, Roza;
  Evrard, J;
  Antony, C;
  St Onge, RP;
  Blondel, M;
  di Rago, Jean-Paul;
  van der Laan, M;
  Steinmetz, Lars M.
• Opis:
  Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to identify pathways of interest. Here we demonstrate that modulating the sorting of nuclear-encoded proteins into mitochondria, mediated by the TIM23 complex, proves therapeutic in both yeast and patient-derived cells exhibiting ATP synthase deficiency. Targeting ​TIM23-dependent protein sorting improves an array of phenotypes associated with ATP synthase disorders, including biogenesis and activity of the oxidative phosphorylation machinery. Our study establishes mitochondrial protein sorting as an intervention point for ATP synthase disorders, and because of the central role of this pathway in mitochondrial biogenesis, it holds broad value for the treatment of mitochondrial diseases.
• Dostępność obiektu:
  Dostęp otwarty
• Data:
  2014.12.18
• Typ:
  Article;
  PeerReviewed
• Język:
  angielski
• Format:
  application/pdf
• Wydawca:
  Nature
• Relacja: http://eprints.ibb.waw.pl/871 ;http://www.ncbi.nlm.nih.gov/pubmed/25519239 ;
  10.1038/ncomms6585
• Temat i słowa kluczowe:
  QD Chemistry;
  QR Microbiology;
  RB Pathology
• Identyfikator: http://eprints.ibb.waw.pl/871/1/NatureCommunic_2014.pdf ;http://eprints.ibb.waw.pl/871/2/NatureCommunic_2014.pdf ;http://eprints.ibb.waw.pl/871/8/NatureCommunic_2014.pdf ;
  Aiyar, Raeka S and Bohnert, M and Duvezin-Caubet, S and Voisset, C and Gagneur, J and Fritsch, ES and Couplan, E and von der Malsburg, K and Funaya, C and Soubigou, F and Courtin, Courtin F and Suresh, Suresh S and Kucharczyk, Roza and Evrard, J and Antony, C and St Onge, RP and Blondel, M and di Rago, Jean-Paul and van der Laan, M and Steinmetz, Lars M. (2014) Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders. Nature Communications, 5 (5585). ISSN 2041-1723
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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