CKII Control of Axonal Plasticity Is Mediated by Mitochondrial Ca²⁺ via Mitochondrial NCLX.

ABSTRACT: Mitochondrial Ca²⁺ efflux by NCLX is a critical rate-limiting step in mitochondria signaling. We previously showed that NCLX is phosphorylated at a putative Casein Kinase 2 (CKII) site, the serine 271 (S271). Here, we asked if NCLX is regulated by CKII and interrogated the physiological implications of this control. We found that CKII inhibitors down-regulated NCLX-dependent Ca²⁺ transport activity in SH-SY5Y neuronal cells and primary hippocampal neurons. Furthermore, we show that the CKII phosphomimetic mutants on NCLX inhibited (S271A) and constitutively activated (S271D) NCLX transport, respectively, rendering it insensitive to CKII inhibition. These phosphomimetic NCLX mutations also control the allosteric regulation of NCLX by mitochondrial membrane potential (Δ

SUBMITTER: Katoshevski T 

PROVIDER: S-EPMC9777275 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature