Small proteins play a large role in cellular energy balance

(2022). DOI: 10.1016 / j.celrep.2022.111204″ width=”800″ height=”530″/>

Graphic abstract. attributed to him: cell reports (2022). DOI: 10.1016 / j.celrep.2022.111204

Scientists at Duke-NUS School of Medicine have discovered new molecular details of how cells ensure they adjust their energy supply to meet energy demand. Their study, which was carried out in collaboration with researchers at the University of Melbourne in Australia and Duke University in Durham, North Carolina, in the United States, sheds light on the critical role microproteins play in assembling larger protein complexes within cells’ energy-generating components known as mitochondria. Their results were published in cell reports.

Mitochondrial problems underlie a wide range of diseases, including common conditions such as heart failure, obesity, diabetes and cancer.

“Our long-term goal is to learn to manipulate the exact proteins that we are investigating to combat them Mitochondrial dysfunction In patients, “Said Senior Investigator Associate Professor Lina Hu, of Duke-NUS Cardiovascular and Metabolic Diseases (CVMD) Program.” The research’s most immediate importance is to reveal new details about how mitochondria function and are maintained in all cells. The work could add an important new level of understanding to this central aspect of cell biology.”

Mitochondria are bounded by a double membrane. The interior of the two membranes hosts a series of proteins that transport electrons along the so-called electron transport chain. This electron transfer is an important part of the processes that extract chemical energy from nutrients and ultimately store it in energy-rich molecules of adenosine triphosphate (ATP).

New insight from the Duke-NUS team reveals that tiny microproteins (also called peptides) play a previously unrecognized role in allowing the formation of the electron transport chain. Specifically, they appear to work together to help and control the assembly of one of the central proteins of the chain, called complex III. This role allows microproteins to participate in the regulation of . levels Electron transport chain proteins, therefore Power supplyin response to changes in Energy Demand.

“Microproteomics have fascinated but also puzzled biologists from various fields for a long time,” co-first author of the study, Liang Chao, who holds a Ph.D. Filter in Duke-NUS. “Our study provides an example of what they can do and how they are involved in controlling energy metabolism at the deepest level of molecular detail.”

“Mitochondria are the batteries and factories of our cells, not only producing energy, but also many of the building blocks Dr. Shan Zhang, a former research fellow in Professor Hu’s Self-Peptides Laboratory, under Duke-NUS’s CVMD program, and now an assistant professor at Zhejiang University, China, said Dr. Shan Zhang, who was previously a research fellow in Professor Hu’s Self-Peptides Laboratory. It is, required for cells to reproduce and survive. We see that modulating levels of these minute proteins can either lead to or protect against mitochondrial dysfunction, a trait that underlies nearly all types of common diseases.”

The team is now planning to move on from these initial results into cellular level To further fully investigate the roles and importance of microproteins in preclinical models and ultimately in humans.

“We hope that these next stages will lead us towards learning how to target the activity of the microprotein to treat mitochondrial diseases,” Professor Hu concluded.

“Innovations in healthcare and disease prevention are capitalizing on advances in knowledge made possible by basic scientific research, such as this study conducted by the assistant professor and her team,” said Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS. “I look forward to seeing where the research leads us next.”

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more information:
Chao Liang et al, Mitochondrial microproteins link metabolic signals with respiratory chain biogenesis, cell reports (2022). DOI: 10.1016 / j.celrep.2022.111204

Introduction of
Duke-NUS Medical College

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