2. Academic Validation
  3. Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition

Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition

  • Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1872-80. doi: 10.1073/pnas.1602264113.
Dipayan Chaudhuri 1,  Daniel J Artiga 2,  Sunday A Abiria 1,  David E Clapham 3
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115;
  • 2 Harvard University, Cambridge, MA 02138;
  • 3 Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115; Department of Neurobiology, Harvard Medical School, Boston, MA 02115 [email protected].
PMID: 26976564 DOI: 10.1073/pnas.1602264113
Abstract

During the mitochondrial permeability transition, a large channel in the inner mitochondrial membrane opens, leading to the loss of multiple mitochondrial solutes and cell death. Key triggers include excessive Reactive Oxygen Species and mitochondrial calcium overload, factors implicated in neuronal and cardiac pathophysiology. Examining the differential behavior of mitochondrial Ca(2+) overload in Drosophila versus human cells allowed us to identify a gene, MCUR1, which, when expressed in Drosophila cells, conferred permeability transition sensitive to electrophoretic Ca(2+) uptake. Conversely, inhibiting MCUR1 in mammalian cells increased the Ca(2+) threshold for inducing permeability transition. The effect was specific to the permeability transition induced by Ca(2+), and such resistance to overload translated into improved cell survival. Thus, MCUR1 expression regulates the Ca(2+) threshold required for permeability transition.

Keywords

Drosophila; H9C2; MCU; cyclophilin D; uniporter.

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