Mitochondrial morphology is regulated by balance of fission and fusion events. Certain dynamin family members such as dynamin-related protein 1 (Drp-1) are involved in the regulation of mitochondrial fission. Drp-1 specifically controls mitochondrial outer membrane fission. However, very little is known about the mechanism that initiates mitochondrial fission by Drp-1. In the present study, we detected Drp-1 was phosphorylated by CaMKI in vitro. In primary cultured hippocampal neurons, high K+ stimulation induced phosphorylated Drp-1 increment and Drp-1 transition from cytoplasm to mitochondria and mitochondrial fragmentation. The effect of high K+ was inhibited by KN93 (CaMK inhibitor). In vitro experiment, we found phosporylation promoted the Drp-1 complexes formation. Although overexpression of GFP-hFis1-C did not alter mitochondrial morphology, it inhibited high K+ induced mitochondrial fission in neurons. These results suggest that Drp-1 dynamics and mitochondrial morphology may be regulated by CaMKI-induced Drp-1 phosphorylation. [J Physiol Sci. 2006;56 Suppl:S109]
