Scientists in Montreal find a new enzymatic complex that can stop cells from aging, breaking the ice to possible brand-new cancer treatments.
Researchers at Université de Montréal and McGill University have actually found a new multi-enzyme complex that reprograms metabolism and overcomes “cellular senescence,” when aging cells stop dividing.
In their study published on September 16, 2021, in Molecular Cell, the researchers reveal that an enzyme complex named HTC (hydride transfer complex) can inhibit cells from aging..
” HTC safeguards cells from hypoxia, an absence of oxygen that usually leads to their death,” said senior author Gerardo Ferbeyre, an UdeM biochemistry teacher and primary scientist at the CRCHUM, the universitys associated teaching healthcare facility proving ground.
” Importantly, HTC can be pirated by specific cancer cells to improve their metabolic process, withstand to a hypoxic environment and proliferate,” stated Ferbeyre, who made the discovery with Sebastian Igelmann, a PhD student in his lab and first author of the research study.
HTC is made up of 3 enzymes: pyruvate carboxylase, malate dehydrogenase 1, and malic enzyme 1. They were all extremely expressed in samples from a prostate cancer mouse design generated at the University of Veterinary Medicine Vienna, in Austria, and in tissue samples from prostate cancer clients.
” Most interestingly, inhibition of these enzymes stopped the growth of prostate cancer cells, suggesting that HTC might be a crucial target to establish brand-new therapies for a range of cancers, including prostate cancer,” said Ferbeyre.
Many crucial metabolic cycles were recognized more than 50 years ago, but HTC remained hidden to researchers. “We found it by performing state-of-the art metabolomic analysis, the study of chemical processes of cell metabolism,” said co-author Ivan Topisirovic, a McGill researcher and medical teacher.
The scientists were able to put together the enzyme complex from cleansed proteins and obtain biophysical data about its composition. Their next action will be to generate a detailed high-resolution structure of the enzyme complex in order to design drugs able to regulate its functions.
Recommendation: “A hydride transfer complex reprograms NAD metabolic process and bypasses senescence” by Sebastian Igelmann, Frédéric Lessard, Oro Uchenunu, Jacob Bouchard, Ana Fernandez-Ruiz, Marie-Camille Rowell, Stéphane Lopes-Paciencia, David Papadopoli, Aurélien Fouillen, Katia Julissa Ponce, Geneviève Huot, Lian Mignacca, Mehdi Benfdil, Paloma Kalegari, Haytham M. Wahba, Jan Pencik, Nhung Vuong, Jordan Quenneville, Jordan Guillon, Véronique Bourdeau, Laura Hulea, Etienne Gagnon, Lukas Kenner, Richard Moriggl, Antonio Nanci, Michael N. Pollak, James G. Omichinski, Ivan Topisirovic and Gerardo Ferbeyre, 16 September 2021, Molecular Cell.DOI: 10.1016/ j.molcel.2021.08.028.