In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis

Carlo Viscomi, Emanuela Bottani, Gabriele Civiletto, Raffaele Cerutti, Maurizio Moggio, Gigliola Fagiolari, Eric A. Schon, Costanza Lamperti, Massimo Zeviani

Research output: Contribution to journalArticlepeer-review


Increased mitochondrial biogenesis by activation of PPAR- or AMPK/PGC-1α-dependent homeostatic pathways has been proposed as a treatment for mitochondrial disease. We tested this hypothesis on three recombinant mouse models characterized by defective cytochrome c-oxidase (COX) activity: a knockout (KO) mouse for Surf1, a knockout/knockin mouse for Sco2, and a muscle-restricted KO mouse for Cox15. First, we demonstrated that double-recombinant animals overexpressing PGC-1α in skeletal muscle on a Surf1 KO background showed robust induction of mitochondrial biogenesis and increase of mitochondrial respiratory chain activities, including COX. No such effect was obtained by treating both Surf1-/- and Cox15-/- mice with the pan-PPAR agonist bezafibrate, which instead showed adverse effects in either model. Contrariwise, treatment with the AMPK agonist AICAR led to partial correction of COX deficiency in all three models, and, importantly, significant motor improvement up to normal in the Sco2KO/KI mouse. These results open new perspectives for therapy of mitochondrial disease.

Original languageEnglish
Pages (from-to)80-90
Number of pages11
JournalCell Metabolism
Issue number1
Publication statusPublished - Jul 6 2011

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology


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