New research on mitochondrial function can play a major role in malignancy

Disorders of the energy supply of cells can cause a number of serious diseases, but they appear to be linked to aging. More research on mitochondrial function is needed to find future cures. A new study by researchers at Karolinska Institutet shows how important molecules within the mitochondria affect their activity in mice and fruit flies. The study, which is published in Advances in science, adding valuable knowledge of previously unexplored protein modifications.

Every cell of the body has an organ called the mitochondrion, which converts nutrients in our food into energy. Mitochondria are an essential part of the metabolism, and when things go wrong we can develop serious diseases.

Mitochondrial dysfunction is a hallmark of a rare genetic disorder but is also seen in common diseases such as diabetes, heart disease, neurodegenerative diseases and the normal aging process.

More research on mitochondria and how they communicate with the rest of the cell is needed if scientists are to find new therapeutic ways to improve mitochondrial function.

Researchers at the Karolinska Institutet, the Max-Planck Institute for Aging Biology in Cologne and the University of California San Diego have now studied how methylation of proteins affects various mitochondrial processes.

Methylation is a chemical modification in which a methyl group (CH3) is added to a molecule, thus potentially affecting its function. S-Adenosylmethionine (SAM), also known as AdoMet, is the major donor of methyl group within the cell, including within mitochondria.

“We are interested in studying this particular molecule since the introduction of SAM changes in cancer and as we age,” says Anna Wredenberg, a researcher at the Department of Biochemistry and Biophysics, Karolinska Institutet.

By removing SAM completely from the mitochondria of fruit flies and mice, the researchers have been able to study which processes in the mitochondria are responsible for methylation.

“Earlier studies have shown that both US and cell energy levels fall as they age. Our study suggests a link between these two pathways by showing that Low SAM levels affect mitochondrial energy production. ”

The study has found out which mitochondrial proteins are methylated and how methylation affects them, and how these changes may affect mitochondrial activity. The researchers also show the physical effects of the lack of such changes. However, a number of questions remain to be answered.

“Our study has shown that some changes can be altered by diet, but we need to continue to explore whether we can change the pathology process for the better,” says Anna Wredenberg. . “So far we have only looked at protein changes, but other molecules can change with SAM within the mitochondrial. We need to study these changes to better understand its role.”

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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. Conflicts of interest are not reported.

Publishing, Anna-Lena Bucher, Yvonne Hinze, Matthew The, Erik Hedman, Ekaterina Chernogubova, Arjana Begzati, Rolf Wibom, Mohit Jain, Roland Nilsson, Lukas Kall, Anna Wedell, Christoph Freyer, Anna Wredenberg. Advances in science, online 19 February 2021.