Ammonia sensitive SLC4A11 mitochondrial uncoupling reduces glutamine induced oxidative stress.

ABSTRACT: SLC4A11 is a NH₃ sensitive membrane transporter with H⁺ channel-like properties that facilitates Glutamine catabolism in Human and Mouse corneal endothelium (CE). Loss of SLC4A11 activity induces oxidative stress and cell death, resulting in Congenital Hereditary Endothelial Dystrophy (CHED) with corneal edema and vision loss. However, the mechanism by which SLC4A11 prevents ROS production and protects CE is unknown. Here we demonstrate that SLC4A11 is localized to the inner mitochondrial membrane of CE and SLC4A11 transfected PS120 fibroblasts, where it acts as an NH₃-sensitive mitochondrial uncoupler that enhances glutamine-dependent oxygen consumption, electron transport chain activity, and ATP levels by suppressing damaging Reactive Oxygen Species (ROS)

SUBMITTER: Ogando DG 

PROVIDER: S-EPMC6604051 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature