Scientists from the University of Technology Sydney have developed molecules that can safely prompt cells to burn more energy and accelerate weight loss. The results of the study were published in the journal Chemical Science.

The researchers focused on mitochondrial uncouplers—substances that alter the way cells produce energy. Under normal conditions, mitochondria convert nutrients into ATP, the cell’s universal “fuel.” Uncouplers disrupt this process: part of the energy is not stored as ATP but is instead dissipated as heat. As a result, cells must burn more fats and other substrates to meet their energy needs.

Such compounds have been known for about a century, but early uncouplers, including 2,4-dinitrophenol (DNP), were extremely toxic. They sharply accelerated metabolism, caused dangerous overheating, and often led to fatal outcomes, which is why they were banned. The main danger of these substances was the very narrow margin between an effective and a harmful dose.

In the new study, the scientists created so-called “mild” uncouplers. The basis was self-limiting conjugates of DNP–triphenylphosphonium (mitoDNP), which are ionic molecules. By modifying their chemical structure, the researchers were able to precisely tune the strength of their effects on mitochondria.

These mild uncouplers increased metabolic activity to a level that cells could tolerate. In addition, the compounds reduced oxidative stress—cell damage caused by reactive oxygen species that is associated with aging.

The researchers emphasize that the development is still at an early stage. Nevertheless, the findings lay the groundwork for creating a new generation of drugs that could gently enhance energy expenditure in people with metabolic disorders and age-related diseases.