A new technology: the production of oxygen within cells

Oxygen is essential for life, and clinicians can provide supplemental oxygen to patients through masks and nasal tubes, but there is currently no way
to deliver oxygen directly to cells.
This ability is initially useful as a research tool, but could eventually have important medical applications — for example, enhancing therapies
that lose their effectiveness when oxygen levels are low.
Researchers at Massachusetts General Hospital (MGH) recently developed a technique that can engineer cells to make oxygen
based on the needs of added chemicals, PNAS reported.

This work was led by Dr.
Vamsi K.
Mootha, professor of systems biology and medicine in the Department of Molecular Biology at MGH, whose lab focuses on mitochondria
.
These special compartments inside the cell produce energy, which requires oxygen to produce energy
.
"We're interested in how mitochondria, cells, and organisms adapt to changes in ambient oxygen," Mootha said
.

Currently, if scientists want to manipulate a cell's oxygen levels in the lab, they place a dish containing the cells in an environmentally controlled room
.
While this is useful, they cannot change the oxygen level
in selected cells at a specific time.

"From this demand came the idea of a genetically coding system that could be deployed in human cells to produce its own oxygen as needed," Mootha said
.

The technique involves the simultaneous expression of a transporter protein and a bacterial enzyme in the cell, which together facilitate the entry of chlorite into the cell and the enzyme of its conversion to oxygen and chlorine
.
The researchers call their new genetic technique SNORCL, the release of supplemental oxygen
from chlorite.
The first generation of SNORCL was able to generate short and moderate pulses of oxygen within the cell in response to the addition of chlorite
.

"Recently, SNORCL has really been used in research to evaluate the role
of oxygen in signaling, metabolism and physiology.
But in the future, SNORCL-based technologies may have multiple clinical uses," Mootha said
.

For example, tumors often have low oxygen levels, which limits the effectiveness of
some anti-cancer therapies.
In such an environment, SNORCL can be used to increase the effectiveness of
these therapies.

Other co-authors include Andrew L.
Markhard, Jason G.
McCoy and Tsz-Leung To
.

Andrew L.
Markhard, Jason G.
McCoy, Tsz-Leung To, Vamsi K.
Mootha.
A genetically encoded system for oxygen generation in living cells.
Proceedings of the National Academy of Sciences, 2022; 119 (43)