mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function
| Autor: | Issam Ben-Sahra, Deborah J. Stumpo, Paul T. Schumacker, Ting Liu, Hsiang-Chun Chang, Hossein Ardehali, Lucía Ramos-Alonso, Konrad T Sawicki, Xinghang Jiang, Sergi Puig, Marina Bayeva, Hidemichi Kouzu, María Teresa Martínez-Pastor, Perry J. Blackshear, Chunlei Chen, Sumeyye Yar, Jason S. Shapiro, Tatsuya Sato |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cardiac response Cardiac function curve Iron-Sulfur Proteins Tristetraprolin Mitochondria Heart Cell Line 03 medical and health sciences Electron Transport Complex III Mice medicine Animals chemistry.chemical_classification Mice Knockout Reactive oxygen species Multidisciplinary NDUFS1 Myocardium NADH Dehydrogenase Iron deficiency Iron Deficiencies medicine.disease Cell biology 030104 developmental biology chemistry PNAS Plus Coenzyme Q – cytochrome c reductase Oxidation-Reduction Function (biology) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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