Even beyond its most obvious consequence – death — oxygen deprivation has profound effects on cells and tissues. A couple of recent papers highlight some connections between epigenetics and hypoxia.
Anaerobic respiration is great for brewing beer. But add O2 and the yeasty beasties stop fermenting. It’s the same principle – only in reverse – in our tissues. Turns out there’s a microRNA (miR-210) that helps to shut down mitochondrial activity by blocking proteins that incorporate non-heme iron into cytochromes and other enzymes. “We’ve found a mechanism that can (at least in part) explain how the cell converts its metabolism under hypoxic conditions from oxidative phosphorylation to anaerobic glycolysis,” says corresponding author Joseph Loscalzo .
This seeming paradox has “a couple of benefits, even though it seems like it would put the cell at a terrible state with respect to available energy sources for normal metabolism,” First¸ the tissue is able to make the best use of the available oxygen. And second, “when they metabolize glucose under glycolysis — even under normoxic conditions — they run less of a risk of making these reactive oxygen species by inefficient mitochondrial metabolism that could be toxic to them.”
The same thing has been observed in cancer cells, where “the teleological reasons are a bit more insidious,” Harvard Med’s Loscalzo notes.
And speaking of cancer …
Researchers at University College Dublin, Ireland have developed a model of the aging prostate by adapting prostate epithelial cells to decreased oxygen levels.
In this study, “our results demonstrate a genome-wide adjustment of DNA methylation and histone acetylation under chronic hypoxic conditions in benign prostate cells and suggest that these phenomena may promote and maintain the hypoxic adaptive pathways that may promote prostate tumour development,” says team Leader Dr. Amanda McCann. “The phenotypic changes that we have observed are characteristics often associated with aggressive cancers such as increased cytokine secretion and increased migratory potential. This may be one of the very first indications that cells can change and become more aggressive.”