Fuhrmann 2018 Cell Mol Life Sci

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Fuhrmann DC, Wittig I, Dröse S, Schmid T, Dehne N, Brüne B (2018) Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia. Cell Mol Life Sci 75:3051-67.

» PMID: 29464284

Fuhrmann DC, Wittig I, Droese S, Schmid T, Dehne N, Bruene B (2018) Cell Mol Life Sci

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 towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B.

Keywords: AKT, Complexome profiling, Hypoxia-inducible factor (HIF), MCIA, Mitochondrial respiration, β-TrCP Bioblast editor: Kandolf G O2k-Network Lab: DE Frankfurt Droese S


Labels: MiParea: Respiration  Pathology: Cancer  Stress:Hypoxia  Organism: Human 

Preparation: Intact cells, Isolated mitochondria 


Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, ROX  HRR: Oxygraph-2k 

Labels, 2018-04