cn9b00341_si_001.pdf (39.24 kB)
Aberrant Decrease of the Endogenous SIRT3 and Increases of Acetylated Proteins in Scrapie-Infected Cell Line SMB-S15 and in the Brains of Experimental Mice
journal contribution
posted on 2019-10-07, 19:49 authored by Adalaiti Maimaitiming, Kang Xiao, Chao Hu, Jia Chen, Xue-Hua Yang, Dong-Hua Zhou, Li-Ping Gao, Xiao-Ping Dong, Qi ShiThe
linkage between mitochondrial dysfunction and neurodegenerative
diseases including prion diseases has been frequently reported. As
the major deacetylase in mitochondria, SIRT3 plays a crucial part
in regulating the function of many mitochondrial proteins. Although
SIRT3 was reported to be linked to several neurodegenerative diseases,
it is still unknown if SIRT3 is involved in prion diseases. In this
study, we have presented a substantially declined status of mitochondrial
SIRT3 in both the levels of cultured cells and an 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 an increase of intracellular ROS and
a reduction of ATP. Furthermore, we have also proposed evidence that
the activity of cellular SIRT3 is partially recovered when abnormal
prion propagation in the cultured cells is removed by resveratrol.
Those data emphasize a close connection between the prion replication
and mitochondrial deacetylation due to SIRT3, thereby partially explaining
mitochondrial dysfunction in prion diseases.