LAUSR

Mitochondrial dysfunction is closely linked to the pathogenesis of neurodegenerative disorders, including prion diseases. SIRT3 is the major mitochondria NAD+ dependent deacetylase that acts as a regulator of mitochondrial protein function. Although SIRT3 was reported to be linked to pathogenesis of neurodegenerative diseases, there is no evidence for the involvement of SIRT3 in prion diseases. In this study, we have demonstrated a declined status of SIRT3 both in the levels of cultured cells and experimental rodent model during scrapie prion replication and infection. Such decreased SIRT3 activity led to a decreased deacetylating activity, resulting in increases of the acetylated forms of some substrates of SIRT3 in cells, such as SOD2 and ATP5β. Declined SOD2 and ATP5β activities subsequently caused increase of intracellular ROS and reduction of ATP. On the other hand, we have also proposed the evidences that removal of prion propagation in the cultured cells by resveratrol partially recovers the cellular SIRT3 activity. Those data highlight a close linkage between the prion replication and mitochondrial deacetylation due to SIRT3, thereby partially explaining mitochondrial dysfunction in prion diseases.