Regulation of Mitochondrial Activities by TRPA1 Channel

While aerobic organisms utilize molecular oxygen (O2) to generate ATP efficiently, cancer cells are known to heavily rely on anaerobic respiration. However, molecular mechanisms underlying the metabolism switching are still elusive. Here we show that an O2 sensing channel TRPA1, which are overexpressed in various types of cancer, regulates mitochondrial activities in cancer cells. Through comprehensive analysis of TRPA1-interacting proteins, we found that TRPA1 associates with several mitochondrial proteins, including NDUFAF4. NDUFAF4 overexpression allowed TRPA1 to be localized into mitochondria. Mitochondrial TRPA1 controlled mitochondrial Ca2+ levels, which affect mitochondrial metabolisms, in response to O2 availability. These results suggest that TRPA1 enables cancer cells to change mitochondrial metabolisms in response to O2 availability through interaction with NDUFAF4.