Drugs that target the way cells convert nutrients into energy could offer new approaches to treating a range of conditions including heart attack and stroke. Using a new way to screen for potential drugs, a team led by Massachusetts General Hospital (MGH) researchers has identified several FDA-approved agents, including an over-the-counter anti-nausea drug, that can shift cellular energy metabolism processes in animals. Their findings, being published online in Nature Biotechnology, may open the door to new therapeutic strategies for several serious health problems.
"Shifts in cells' energy production pathways take place naturally during development and in response to demanding activities like sprinting versus long-distance running. They are also known to be involved in several disease states," explains Vamsi Mootha, MD, of the MGH Center for Human Genetic Research, who led the study. "We wanted to identify compounds that can safely induce this shift those that have previously been discovered are too toxic and investigate their therapeutic potential in animal models."
Normally cells convert nutrients into energy by relying on two cellular processes. One involves the uptake of sugars that are broken down in the cytoplasm into a molecule called lactate via a process called glycolysis, which quickly yields a small amount of ATP, the enzyme that provides cellular energy. Alternatively, sugars and proteins can be processed in cellular structures called mitochondria to release greater amounts of ATP through a more efficient process called cellular respiration.
In cancer cells and other rapidly proliferating cells, energy is produced predominantly by glycolysis, suggesting that a shift away from that mechanism might suppress tumor growth. Previous animal studies suggested that a reduction in mitochondrial respiration could mimic a process called ischemic preconditioning, in which brief episodes of ischemia a reduction i
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Massachusetts General Hospital