Researchers at the Wistar Institute in Philadelphia have discovered that mice that lack the TRAP-1 protein live longer and suffer less from age-related illnesses. Their findings were published yesterday in the open-access journal Cell Press. According to the authors, Sofia Lisanti and colleagues, TRAP-1 could possibly be used in the future, as a target for anti-cancer treatment.
TRAP-1 is a so-called chaperone protein, a protein that folds other proteins into the right configuration for them to perform their function. In healthy cells TRAP-1 is involved in the energy production by mitochondria. Cancer cells overexpress TRAP-1 and use the protein to survive a therapeutic attack. Lisanti and her colleagues developed mice that don’t have any TRAP-1, a TRAP-1 knockout mouse, and studied the effects of this deficiency on the development of these mice. The researchers expected to see negative effects on the health of the mice. "We usually link the reprogramming of metabolic pathways with human diseases, such as cancer", Lisanti explained.
To their surprise, the researchers observed that the knockout mice lived longer and suffered less from age-related illnesses like tissue degeneration, obesity, and spontaneous tumor formation. The TRAP-1 deficiency caused mitochondrial proteins to be wrongly folded. Subsequently, the cell upregulates its mitochondrial activity, causing more oxidative stress and the associated DNA damage. While DNA damage may seem counterproductive to longevity and good health, the low level of DNA damage actually reduces cell proliferation, thereby stimulating the natural repair mechanisms of the cell.
“In this study we have proven that TRAP-1 is a protein that can cause cancer. This is an important finding because TRAP-1 can function as a target for anti-cancer treatment”, says Lisanti. Actually, in her lab in Philadelphia the researcher and her colleagues have already developed an effective anti-cancer drug that has very little side effects.
Sources: Wistar Institute en Cell Press