Mitochondrial Ca²⁺ Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity.

ABSTRACT: Ca²⁺ dynamics and oxidative signaling are fundamental mechanisms for mitochondrial bioenergetics and cell function. The MCU complex is the major pathway by which these signals are integrated in mitochondria. Whether and how these coactive elements interact with MCU have not been established. As an approach toward understanding the regulation of MCU channel by oxidative milieu, we adapted inflammatory and hypoxia models. We identified the conserved cysteine 97 (Cys-97) to be the only reactive thiol in human MCU that undergoes S-glutathionylation. Furthermore, biochemical, structural, and superresolution imaging analysis revealed that MCU oxidation promotes MCU higher order oligomer formation. Both oxidation and mutation of MCU Cys-97 exhibited persistent MCU channel activity with

SUBMITTER: Dong Z 

PROVIDER: S-EPMC5357178 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature