Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism. (https://pubmed.ncbi.nlm.nih.gov/38215760/)

These scientists wanted to understand how certain genetic mutations can cause neurological diseases in mice. They focused on a part of the cells called the electron transport chain (ETC), which helps produce energy. They found that when there is a problem with a specific part of the ETC called complex I, the mice get sick.

But they discovered something interesting - when the mice were put in a low-oxygen environment (called hypoxia), their disease was actually improved. The scientists wanted to figure out why this happened.

To do this, they studied a tiny worm called C. elegans, which has similar complex I as mice. They found that when they made mutations in complex I of the worms, just like in the mice, the worms also got sick. But when they put the sick worms in a low-oxygen environment, they became healthier again.

The scientists then looked for other mutations in a specific part of complex I called NDUFA6/nuo-3. They found that when they made a specific mutation called NDUFA6/nuo-3(G60D), it had the same effect as putting the worms in a low-oxygen environment - it made the sick worms healthy again.

They also discovered that the oxygen-sensitive part of complex I, which is like a pocket that holds a molecule called ubiquinone, was important for this rescue. When they made mutations in this pocket, the NDUFA6/nuo-3(G60D) mutation or low-oxygen environment couldn't help the sick worms anymore.

So, the scientists found that there is a special connection between the NDUFA6/nuo-3 part of complex I and the pocket that holds ubiquinone. This connection can help fix the problems caused by the genetic mutations, just like being in a low-oxygen environment.

Meisel JD., Miranda M., Skinner OS., Wiesenthal PP., Wellner SM., Jourdain AA., Ruvkun G., Mootha VK. Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism. Cell. 2024 Feb 1;187(3):659-675.e18. doi: 10.1016/j.cell.2023.12.010. Epub 2024 Jan 11.