实验室署名论文

 Abstract: Loss of the mitochondrial protease activity of Omi causes  mitochondrial dysfunction, neurodegeneration with parkinsonian features  and premature death in mnd2 (motor neuron degeneration 2) mice.  However, the detailed mechanisms underlying this pathology remain  largely unknown. Here, we report that Omi participates in the process of  mitochondrial biogenesis, which has been linked to several  neurodegenerative diseases. The mitochondrial biogenesis is deficit in  mnd2 mice, evidenced by severe decreases of mitochondrial components,  mitochondrial DNA and mitochondrial density. Omi cleaves  lycogen  synthase kinase 3b (GSK3b), a kinase promoting PPARc coactivator-1a  (PGC-1a) degradation, to regulate PGC-1a, a factor important for the  mitochondrial biogenesis. In mnd2 mice, GSK3b abundance is increased and  PGC-1a abundance is decreased significantly. Inhibition of GSK3b by  SB216763 or overexpression of PGC-1a can restore mitochondrial  biogenesis in mnd2 mice or Omiknockdown N2a cells. Furthermore, there is  a significant improvement of the movement ability of mnd2 mice after  SB216763 treatment. Thus, our study identified Omi as a novel regulator  of mitochondrial biogenesis, involving in Omi protease-deficientinduced  neurodegeneration.