Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia.

Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia. Cell Mol Life Sci. 2018 Feb 20;: Authors: Fuhrmann DC, Wittig I, Dröse S, Schmid T, Dehne N, Brüne B Abstract 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 tow...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research

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Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
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Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
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Source: Radiation and Environmental Biophysics - Category: Physics Authors: Tags: Radiat Environ Biophys Source Type: research
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Source: Iranian Journal of Microbiology - Category: Microbiology Tags: Iran J Microbiol Source Type: research
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Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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