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

Cellular and Molecular Life Sciences : CMLS
Dominik Christian FuhrmannBernhard Brüne

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 toward...Continue Reading

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Citations

Feb 14, 2019·Journal of Cellular Physiology·Javad MahmoudiSiamak Sandoghchian Shotorbani
May 1, 2019·Antioxidants & Redox Signaling·Anna StepanovaAlexander Galkin
Jan 2, 2019·Nature Structural & Molecular Biology·Andrew M HartleyAmandine Maréchal
Oct 7, 2020·The FEBS Journal·Yanli BiYongchao Zhao
Dec 16, 2020·Angewandte Chemie·Gabriele GiachinMontserrat Soler-Lopez
Jan 9, 2021·Biochimica Et Biophysica Acta. Bioenergetics·Karolina Szczepanowska, Aleksandra Trifunovic
Aug 8, 2021·International Journal of Molecular Sciences·Ilka Wittig, Pedro Felipe Malacarne
Oct 8, 2021·Metabolic Brain Disease·Xiaoyin WangXunming Ji

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Methods Mentioned

BETA
electrophoresis
ChIP
ubiquitination
immunoprecipitation
pull down
FCS
protein assay
coIP
PCR

Software Mentioned

DCMSLink
NetPhos
genome
NOVA
MCIA
Image Studio Digits

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