Cellular respiration is a highly complex and regulated process that allows cells to draw energy from nutrition. An international team of scientists in Finland, Germany and Poland investigated the important role of long-chain fatty acids in directing this process. Results published in Nature Communicationswill shed light on the understanding of mitochondrial function involving perturbations of cellular energy metabolism.
They are small, highly efficient energy factories that run inside our cells. Often referred to as the “workforce,” the mitochondria extract most of the cellular energy from nutrition. Researchers from the University of Oulu (Finland), the Heidelberg Institute for Theoretical Studies (HITS, Germany), and the University of Warsaw (Poland) have succeeded in demonstrating how long-chain fatty acids regulate the amount of energy withdrawn in this diet. A process called cellular respiration. This discovery is groundbreaking since the importance of long-chain fatty acids produced by mitochondria in cellular respiration was not previously known and the results open up an entirely new approach.
“This information helps us understand diseases involving dysfunction of mitochondria and cellular respiration much better than before,” says M. Tanvir Rahman of the University of Oulu and lead author on the paper.
The study is part of a more comprehensive research project looking at the relationship between cellular respiration and the nutritional status of the cell. The scientists used a protein engineering method, designing mutants of a so-called MECR enzyme involved in mitochondrial fatty acid synthesis using computational molecular modeling, along with structure determination by crystallography, and other experiments to validate the predictions. “Our study is a successful case example of targeted protein modification,” says researcher Kaija Autio from the University of Oulu.
The experiments in this interdisciplinary study were performed by biochemists and crystallographers from the Faculty of Biochemistry and Molecular Medicine of the University of Oulu and the Biocentre Oulu, while the molecular modeling was performed by computational biophysicists from the Heidelberg Institute for Theoretical Studies (HITS) and the University of Warsaw. “This study really demonstrates the value of combining computational and experimental approaches to uncover complex biomolecular mechanisms,” says Rebecca Wade of HITS.
Tanveer-Rahman et al., A geometric variant of a MECR reductase that reveals the indispensability of long-chain acyl-ACPs for mitochondrial respiration, Nature Communications (2023). DOI: 10.1038/s41467-023-36358-7
Provided by Heidelberger Institut für Theoretische Studien gGmbH
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