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


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.

SUBMITTER: Chaudhuri D 

PROVIDER: S-EPMC4822583 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Chaudhuri Dipayan D   Artiga Daniel J DJ   Abiria Sunday A SA   Clapham David E DE  

Proceedings of the National Academy of Sciences of the United States of America 20160314 13


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 Droso  ...[more]

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