Newswise — NEW BRUNSWICK, NJ -- Nutrients from food provide fuel to cells within the body so they may function, grow and multiply. A team of scientists at Rutgers Robert Wood Johnson Medical School is working to understand the science behind this process to determine how nutrients affect both healthy and diseased cells. The laboratory’s latest study has found a potential target that may help to control how nutrients feed cells in cancer, diabetes and other age and metabolic-related disorders.
Led by Estela Jacinto, PhD, principal investigator and associate professor of biochemistry and molecular biology at the medical school, the researchers have been studying how the protein, mTOR, helps to regulate cell machinery, which drives the growth of every cell in the body. As cells break down nutrients during metabolism, they create metabolic products called metabolites, which serve as fuel and building blocks to make more cells. Previous studies have found that when there are sufficient nutrients, mTOR promotes cell growth. In this new study, released online today in Molecular Cell, they discovered that mTOR also responds to decreasing levels of nutrients, acting as “traffic control” to help stabilize cells as nutrient intake fluctuates.
“Similar to a traffic control officer, mTOR has the ability to sense road conditions and direct metabolic products through the pathways that feed cells,” said Dr. Jacinto. “However, there is a dysfunction of this process in cancer and other disorders, as traffic through the pathways becomes heavy, alternate routes emerge and traffic control becomes poorly enforced.”
Specifically, Dr. Jacinto’s lab discovered that when glucose availability is limited, mTOR responds by mobilizing the amino acid glutamine, which serves as an alternative to glucose. Metabolism of glutamine enables the cells to survive under glucose starvation. Although it is known that disruption in glucose and glutamine metabolism plays a role in diabetes, cancer, osteoarthritis and aging, this is the first study to indicate that mTOR actively participates in the process to restore cell stability when there are not enough nutrients to fuel cell growth.
“Gaining insight on how mTOR controls metabolite traffic could be used to develop new therapeutic strategies for cancer, as well as for aging- and metabolic-related conditions such as diabetes, obesity, as well as autoimmune disorders,” said Dr. Jacinto.
Along with Dr. Jacinto, the research was conducted by Joseph G. Moloughney, Peter K. Kim and Nicole M. Vega-Cotto, all co-first authors from the Department of Biochemistry and Molecular biology at Rutgers Robert Wood Johnson Medical School. Chang-Chih Wu, Matthew Adlam, Thomas Lynch, Po-Chien Chou and Guy Werlen from the department also contributed, as did Sisi Zhang and Joshua D. Rabinowitz of the Lewis-Sigler Institute for Integrative Genomics at Princeton University.
The research was supported by grants for the National Institutes of Health (GM079176 and CA154674), a Stand Up to Cancer Innovative Research grant (grant SU2C-AACR-IRG0311); a New Jersey Commission for Cancer Research grant; a research supplement to promote diversity in health-related research (CA-154674-04S1); and NIH grant CA163591 and the SU2C Pancreatic Cancer Dream Team.
About Rutgers Robert Wood Johnson Medical School As one of the nation's leading comprehensive medical schools, Robert Wood Johnson Medical School, part of Rutgers, The State University of New Jersey, is dedicated to the pursuit of excellence in education, research, health care delivery, and the promotion of community health. In cooperation with Robert Wood Johnson University Hospital, the medical school's principal affiliate, they comprise New Jersey's premier academic medical center. In addition, Robert Wood Johnson Medical School has 34 other hospital affiliates and ambulatory care sites throughout the region.
Robert Wood Johnson Medical School encompasses 21 basic science and clinical departments, and hosts centers and institutes including The Cardiovascular Institute, the Child Health Institute of New Jersey, the Women's Health Institute. The medical school maintains educational programs at the undergraduate, graduate, and postgraduate levels for more than 1,500 students on its campuses in New Brunswick and Piscataway, and provides continuing education courses for health care professionals and community education programs. To learn more about Robert Wood Johnson Medical School, visit rwjms.rutgers.edu. Find us online at facebook.com/RWJMedicalSchool and twitter.com/RWJMS.
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