Aims: To preserve energy, ATP-consuming processes such as Na/K-ATPase and protein synthesis are decreased in hypoxia. In lung alveolar epithelial cells, this is also associated with decreased cellular O2-consumption and decreased activity of complexes 1, 2 and 3 of the mETC. To understand possible mechanisms we tested, whether the decreased respiratory activity might be associated with altered expression of mETC enzymes. We chose subunits of mETC proteins which are encoded in the nuclear or the mitochondrial genome. In addition, we studied potential regulators of their expression. Methods: Confluent human A549 cells were exposed to hypoxia (1.5% and 5% O2). mRNA expression was measured by qRT-PCR using 28S rRNA for normalization. Results: Severe hypoxia (1.5% O2) for 24h and 48h decreased the mRNA expression of the nuclear-encoded NDUFS8 of complex 1 and SDHB of complex 2. Also the messages for the mitochondrial encoded cytochrome B, cytochrome oxidase-1, and ATPase-6 were decreased. At 5% O2, there was a decrease in mRNA expression after 24h but recovery thereafter. These changes were paralleled by a transient decrease (5% O2, 24h) and pronounced decrease (1.5% O2, 24h, 48h) of TFAM, a key activator of mitochondrial transcription. 1.5% O2 had no effect on AMP- kinase, PPAR, NRF-1 and NRF-2, whereas the mRNA- expression of these factors appeared up-regulated after 48h at 5% O2. Conclusion: These results indicate that decreased respiration of A549 cells in severe hypoxia is associated with a decreased expression of key enzymes of the mETC, which is probably caused by decreased TFAM.