C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD⁺ cleavage activity to inhibit mitochondrial respiration.

ABSTRACT: Mitochondrial dysfunction is a key pathological feature of many different types of neurodegenerative disease. Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) has been attracting much attention as an important molecule for inducing axonal degeneration and neuronal cell death by causing loss of NAD (NADH). However, it has remained unclear what exactly regulates the SARM1 activity. Here, we report that NAD⁺ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD⁺ cleavage. Nonphosphorylatable mutation of Ser-548 o

SUBMITTER: Murata H 

PROVIDER: S-EPMC6295714 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature