CaMKII (Ca²⁺/Calmodulin-Dependent Kinase II) in Mitochondria of Smooth Muscle Cells Controls Mitochondrial Mobility, Migration, and Neointima Formation.

ABSTRACT:

Objective

The main objective of this study is to define the mechanisms by which mitochondria control vascular smooth muscle cell (VSMC) migration and impact neointimal hyperplasia.

Approach and results

The multifunctional CaMKII (Ca²⁺/calmodulin-dependent kinase II) in the mitochondrial matrix of VSMC drove a feed-forward circuit with the mitochondrial Ca²⁺ uniporter (MCU) to promote matrix Ca²⁺ influx. MCU was necessary for the activation of mitochondrial CaMKII (mtCaMKII), whereas mtCaMKII phosphorylated MCU at the regulatory site S92 that promotes Ca²⁺ entry. mtCaMKII was necessary and sufficient for platelet-derived growth factor-induced mitochondrial Ca²⁺ uptake. This effect was dependent on MCU. mtCaMKII and MCU in

SUBMITTER: Nguyen EK 

PROVIDER: S-EPMC5970052 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature