Article
Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension.
EMBO molecular medicine - 1 Jun 2015
White Kevin, Lu Yu, Annis Sofia, Hale Andrew E, Chau B Nelson, Dahlman James E, Hemann Craig, Opotowsky Alexander R, Vargas Sara O, Rosas Ivan, Perrella Mark A, Osorio Juan C, Haley Kathleen J, Graham Brian B, Kumar Rahul, Saggar Rajan, Saggar Rajeev, Wallace W Dean, Ross David J, Khan Omar F, Bader Andrew, Gochuico Bernadette R, Matar Majed, Polach Kevin, Johannessen Nicolai M, Prosser Haydn M, Anderson Daniel G, Langer Robert, Zweier Jay L, Bindoff Laurence A, Systrom David, Waxman Aaron B, Jin Richard C, Chan Stephen Y
Abstract excerpt
Iron-sulfur (Fe-S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR-210-ISCU1/2 axis cause Fe-S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR-210 and repression of the miR-210 targets ISCU1/2 down-regulated Fe-S levels. In...
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