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Generating Oxygen Within Cells

Researchers at Massachusetts General Hospital (MGH) have developed a never-before-seen method to generate oxygen molecules within cells.

Oxygen is essential for aerobic respiration, which releases energy required for life processes. To address an oxygen deficiency, current technologies to resolve this issue include oxygen delivery through face masks and nasal tubes, but unfortunately, no methods have been developed for the direct delivery of oxygen into cells.

Fortunately, researchers from Massachusetts General Hospital (MGH) have successfully developed a method to stimulate oxygen generation within the cell itself, by exposing it to a chemical. Besides its novel uses for research, this work may allow for the future development of methods to maintain optimal oxygen levels for medical treatments to ensure the best therapeutic results.

This research was led by Vamsi K. Mootha, MD, a Professor of Systems Biology and Medicine in the Department of Molecular Biology at MGH, whose lab’s research focus is mitochondria. Mitochondria are commonly known as the powerhouses of the cell as they produce chemical energy in the presence of oxygen. In particular, Mootha’s lab is interested in how cells, their mitochondria, and organisms as a whole adapt to changes in oxygen levels.

With current technology, researchers may only manipulate oxygen levels in the lab by placing the target in an environmentally controlled chamber. Though relatively effective, they are unable to manipulate oxygen levels in the cells at a specific and desired time.

“From this need came the idea for a genetically encoded system that could be deployed in human cells to produce their own oxygen on demand,” said Mootha.

Their method involved the simultaneous expression of a transporter, which helps the cell uptake the required materials for oxygen production, and chlorite O2-lyase, also known as chlorite dismutase (Cld)— an enzyme of bacterial origin that converts chlorite ions (ClO-2) into oxygen (O2) and chloride ions (Cl).

The team named their new technology SNORCL, short for Supplemental Oxygen Released from Chlorite. It was able to produce short and sufficient pulses of oxygen inside cells after their exposure to ClO-2.

“In the near-term SNORCL is really for the research arena, for evaluating the role of oxygen in signalling, metabolism, and physiology in great detail. But then in the future, technologies based on SNORCL could have a variety of clinical uses,” said Mootha.

For example, some cancer treatments have limited effectiveness in the low-oxygen environment of cancer tumours. Thus, SNORCL may be used together with anticancer therapies to improve their effectiveness in these environments. [APBN]

Source: Markhard et al. (2022). A genetically encoded system for oxygen generation in living cells. Proceedings of the National Academy of Sciences, 119(43), e2207955119.