Credit: Karolinska Institute.
Disturbances in the energy supply to cells can cause a number of serious diseases, but they also appear to be linked to aging. More research on mitochondrial function is needed to find future therapies. A new study co-authored by researchers at Karolinska Institutet shows how an important molecule within mitochondria affects their function in mice and fruit flies. The study published in Science Advances, Adds valuable knowledge of previously relatively undiscovered protein modifications.
In every cell of the body there is an organ called mitochondria, which turns the nutrients in our food into energy. Mitochondria are an essential part of metabolism, and when things go wrong, they can become seriously ill.
Mitochondrial dysfunction is the hallmark of a group of rare genetic disorders but it can also be observed in common diseases such as diabetes, heart disease, neurodegenerative diseases and the normal aging process.
More research is needed on mitochondria and how they communicate with the rest of the cell if scientists want to find new therapies to improve mitochondrial function.
Researchers at the Karolinska Institute and the Max Planck Institute for Aging Biology in Cologne and the University of California at San Diego studied how protein methylation affects different mitochondrial processes.
Methyl is a chemical modification in which a methyl group (CH3) is added to a molecule, which could affect its function. S-Adenosylmethionine (SAM), also known as AdoMet, is the main donor of the methyl group inside the cell, including within the mitochondria.
“We are interested in studying this particular molecule since the emergence of SAM changes in cancer and as we age,” says Anna Wredenberg, a researcher in the Department of Medicinal Biochemistry and Biophysics, Karolinska Institutet.
By completely removing SAM from the mitochondria of fruit flies and mice, the researchers were able to study processes in methylation-dependent mitochondria.
Previous studies have shown that both SAM and cellular energy levels decline during aging. Our study suggests a link between these two pathways by demonstrating that low SAM levels can affect mitochondrial energy production. ”
The study identified which mitochondrial proteins are methylated and how methylated affects them, and how these alterations might affect mitochondrial function. Researchers also elucidate the physiological consequences of not having such changes. However, many questions remain to be answered.
“Our study provided an indication that some alterations can be modified through diet,” says Anna Wredenberg. “But we need to continue screening if we can alter the disease process for the better.” “So far, we have only considered protein changes, but other molecules can also be modified by SAM within mitochondria. We have to study these modifications to get a better understanding of the role they play.”
The study was funded by the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Max Planck Society and the Ragnar Söderberg Foundation. No conflicts of interest have been reported.
Publication: “The Single Carbon Complex Controls Mitochondrial Energy Metabolism Via Complex 1 and Iron-Sulfur Group”, Florian A. Schauber, David Moore, Elian Atanasoff, Marco F Moidas, Paula Clemente, Akos Vigvari, Naglaa Al-Faisi, Roberta Filograna, Anna Lina Boucher, Yvonne Haines, Matthew The, Eric Heidman, Ekaterina Chernjoobova, Ariana Bigzati, Rolfe Weibum, Mohit Jain, Nelson, Lucas Cale, Anna Weddell, Christoph Fryer, Anna Widdenberg. Science AdvancesOnline February 19, 2021.