Scientists Discover How Excess Oxygen Damages Cells

Scientists at Gladstone Institutes have discovered a chemical process that can damage cells and tissues when exposed to high levels of oxygen, known as hyperoxia or oxygen toxicity. The study found that excess oxygen changes proteins in cells that contain iron and sulfur in a chemical process similar to the rusting of iron. The “rusty” proteins then trigger a chain reaction that damages cells and tissues. The research, published in the journal Molecular Cell, has implications for conditions such as heart attacks and sleep apnea.

The effects of hyperoxia have been relatively understudied compared to the details of how oxygen shortage impacts cells and tissues, which has been studied for many years. The study found that the use of antioxidants, which can combat reactive oxygen species, is unlikely to be sufficient to prevent oxygen toxicity.

The researchers utilized CRISPR genome editing to test the roles of various genes in hyperoxia. They removed more than 20,000 different genes from human cells grown in the lab and compared the growth of each group of cells at 21% and 50% oxygen. Four molecular pathways stood out in the screen as being involved in the effects of hyperoxia. They related to diverse cellular functions, including the repair of damaged DNA, the production of new DNA building blocks, and the generation of cellular energy.

The team discovered that each pathway had a critical protein that contained iron atoms connected to sulfur atoms, known as “iron-sulfur clusters,” in its molecular structure. In as little as 30% oxygen, the iron-sulfur clusters in the four proteins become oxidized, chemically reacting with oxygen atoms and causing the proteins to degrade. As a result, cells stop functioning correctly and consume even less oxygen, causing a further increase in oxygen levels in the surrounding tissues.

The study found that the electron transport chain (ETC) is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional iron-sulfur cluster pathways.

The findings shed light on how excess oxygen can cause organ damage, seizures, and death, particularly if it’s in excess of the body’s oxygen needs. This research provides a specific timeline for what happens in hyperoxia and gives a deeper understanding of the mechanisms behind the phenomenon.