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Chronic hypoxia alters mitochondrial composition in human macrophages.

Authors
  • Fuhrmann, Dominik Christian1
  • Wittig, Ilka
  • Heide, Heinrich
  • Dehne, Nathalie
  • Brüne, Bernhard
  • 1 Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, 60590 Frankfurt, Germany. , (Germany)
Type
Published Article
Journal
Biochimica et Biophysica Acta
Publisher
Elsevier
Publication Date
Dec 01, 2013
Volume
1834
Issue
12
Pages
2750–2760
Identifiers
DOI: 10.1016/j.bbapap.2013.09.023
PMID: 24140568
Source
Medline
Keywords
License
Unknown

Abstract

Hypoxia inducible factors (HIFs) are important mediators of the cellular adaptive response during acute hypoxia. The role of HIF-1 and HIF-2 during prolonged periods of hypoxia, i.e. chronic hypoxia is less defined. Therefore, we used human THP-1 macrophages with a knockdown of either HIF-1α, HIF-2α, or both HIFα-subunits, incubated them for several days under hypoxia (1% O2), and analyzed responses to hypoxia using 2D-DIGE coupled to MS/MS-analysis. Chronic hypoxia was defined as a time point when the early but transient accumulation of HIFα-subunits and mRNA expression of classical HIF target genes returned towards basal levels, with a new steady state that was constant from 72h onwards. From roughly 800 spots, that were regulated comparing normoxia to chronic hypoxia, about 100 proteins were unambiguously assigned during MS/MS-analysis. Interestingly, a number of glycolytic proteins were up-regulated, while a number of inner mitochondrial membrane proteins were down-regulated independently of HIF-1α or HIF-2α. Chronic hypoxic conditions depleted the mitochondrial mass by autophagy, which occurred independently of HIF proteins. Macrophages tolerate periods of chronic hypoxia very well and adaptive responses occur, at least in part, independently of HIF-1α and/or HIF-2α and comprise mitophagy as a pathway of particular importance.

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