Cell Image of the Month: TRAP1 is a regulator of tumor cell metabolism

Image of TRAP1 showing its localization to mitochondria in MCF7 cells.

"Movember" marks the time of the year when men around the world grow their moustaches to raise awareness for men's health issues, such as prostate cancer, the second most common cancer in men and one of the leading causes of death in men worldwide. (Rawla et al, 2019)

In this image of the month, we want to highlight the role of the mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor associated protein 1), a protein which is highly abundant in prostate cancer compared to healthy prostate. TRAP1 was recently identified as a driver for prostate cancer development and proposed as a new potential drug target for this disease (Lisanti et al, 2016).

TRAP1 localizes to the mitochondria, where it plays an important role in the regulation of energy metabolism. But how does this impact the development of cancer? One of the hallmarks of cancer is that cancer cells usually obtain their energy in a different way than normal cells. This metabolic shift is known as the Warburg effect. Sciacovelli et al showed that high levels of TRAP1 inhibit Succinate dehydrogenase (SDH), an important enzyme in the citric acid cycle. This interaction shuts down the citric acid cycle, which is responsible for most of the energy production in healthy cells. This allows the cancer cells to reprogram their energy production, which enhances the Warburg effect and increases their metastatic potential.

However, the exact role of TRAP1 is still controversial. Its exact function seems to be tumor and context dependent and further research is necessary to fully understand the role of this multifunctional protein (Matassa et al, 2018).

Christian Gnann