These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Mitochondrial Ca2+ Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity.
    Author: Dong Z, Shanmughapriya S, Tomar D, Siddiqui N, Lynch S, Nemani N, Breves SL, Zhang X, Tripathi A, Palaniappan P, Riitano MF, Worth AM, Seelam A, Carvalho E, Subbiah R, Jaña F, Soboloff J, Peng Y, Cheung JY, Joseph SK, Caplan J, Rajan S, Stathopulos PB, Madesh M.
    Journal: Mol Cell; 2017 Mar 16; 65(6):1014-1028.e7. PubMed ID: 28262504.
    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 higher [Ca2+]m uptake rate, elevated mROS, and enhanced [Ca2+]m overload-induced cell death. In contrast, these effects were largely independent of MCU interaction with its regulators. These findings reveal a distinct functional role for Cys-97 in ROS sensing and regulation of MCU activity.
    [Abstract] [Full Text] [Related] [New Search]