Sesn2 Serves as a Regulator between Mitochondrial Unfolded Protein Response and Mitophagy in Intervertebral Disc Degeneration.

ABSTRACT: Mitochondrial unfold protein response (UPR^mt) can induce mitophagy to protect cell from unfold protein. However, how UPR^mt induces mitophagy to protect cell is not yet clear. Herein, Sesn2 was considered to be a key molecule that communicated UPR^mt and mitophagy in the intervertebral disc. Silencing of Sesn2 was able to reverse the protective effects of Nicotinamide riboside (NR) on nucleus pulposus (NP) cells and inhibit mitophagy induced by UPR^mt. UPR^mt upregulated Sesn2 through Eif2ak4/eIF2α/Atf4, and further induced mitophagy. Sesn2 promoted the translocation of cytosolic Parkin and Sqstm1 to the defective mitochondria respectively, thereby enhancing mitophagy. The translocation of cytosolic Sqstm1 to the defective mitochondria was

SUBMITTER: Xu WN 

PROVIDER: S-EPMC9830501 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature