MICU1 imparts the mitochondrial uniporter with the ability to discriminate between Ca²⁺ and Mn²⁺.

ABSTRACT: The mitochondrial uniporter is a Ca²⁺-activated Ca²⁺ channel complex that displays exceptionally high conductance and selectivity. Here, we report cellular metal toxicity screens highlighting the uniporter's role in Mn²⁺ toxicity. Cells lacking the pore-forming uniporter subunit, MCU, are more resistant to Mn²⁺ toxicity, while cells lacking the Ca²⁺-sensing inhibitory subunit, MICU1, are more sensitive than the wild type. Consistent with these findings, Caenorhabditis elegans lacking the uniporter's pore have increased resistance to Mn²⁺ toxicity. The chemical-genetic interaction between uniporter machinery and Mn²⁺ toxicity prompted us to hypothesize that Mn²⁺ can indeed be transported by the un

SUBMITTER: Kamer KJ 

PROVIDER: S-EPMC6112746 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature