mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function.
Proc Natl Acad Sci U S A
; 115(27): E6291-E6300, 2018 07 03.
Article
en En
| MEDLINE
| ID: mdl-29915044
ABSTRACT
Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp display cardiac dysfunction with iron deficiency, demonstrating that TTP is necessary for maintaining cardiac function in the setting of low cellular iron. Altogether, our results describe a pathway that is activated in iron deficiency to regulate mitochondrial function to match the availability of Fe/S clusters.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tristetraprolina
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Deficiencias de Hierro
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Proteínas Hierro-Azufre
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Mitocondrias Cardíacas
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Miocardio
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NADH Deshidrogenasa
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article