Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia
| العنوان: | Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia |
|---|---|
| المؤلفون: | Bernhard Brüne, Dominik C. Fuhrmann, Stefan Dröse, Ilka Wittig, Tobias Schmid, Nathalie Dehne |
| المصدر: | Cellular and Molecular Life Sciences. 75:3051-3067 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cellular adaptation, THP-1 Cells, Respiratory chain, Mitochondrion, 03 medical and health sciences, Cellular and Molecular Neuroscience, Oxygen Consumption, Cell Line, Tumor, medicine, Humans, Amino Acid Sequence, Molecular Biology, Protein kinase B, TMEM126B, Pharmacology, chemistry.chemical_classification, DNA ligase, Electron Transport Complex I, Chemistry, Membrane Proteins, Cell Biology, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, Transmembrane protein, Mitochondria, Cell biology, 030104 developmental biology, Proteolysis, Molecular Medicine, RNA Interference, medicine.symptom |
| الوصف: | Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B. |
| تدمد: | 1420-9071 1420-682X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee8456cff720ceba0e95550d6c1057c0 https://doi.org/10.1007/s00018-018-2779-y |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ee8456cff720ceba0e95550d6c1057c0 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14209071 1420682X |
|---|