The mitochondrial peroxiredoxins directly bind to Cyclophilin D and regulates mitochondrial membrane potential

Abstract

Peroxiredoxins (Prx) are the family of antioxidants that efficiently scavenge peroxides. Prxs have characteristics that distinguish them from conventional ROS scavenging antioxidants, such as the hyper oxidized state in the presence of excess peroxide or the capability to form oligomeric structures. These characters affect to the redox sensors that transmit the signals as the cellular response to oxidative stress. Prxs are abundantly existed in diverse locations of cellular organelles include the cytosol, lysozyme, mitochondria and nucleus, etc. Interestingly, in many cases Prxs in the mitochondria of tumors are highly expressed. It seems that the way of overcoming the highly expressed ROS generation caused by abnormal cell growth. In addition, the high levels of antioxidant proteins assign protection against ROS generations caused by therapeutic treatments. This phenomenon tell us that Prx have the potential of anticancer drugs target. The Cyclophilin D (CypD), the protein in the mitochondrial matrix and one of the core proteins of mitochondrial permeability transition pore (MPTP), are highly expressed in many type of tumors, but the function and mechanisms are currently unclear. CypD are also responds to ROS generation in the mitochondria. Moreover, I confirmed that the CypD have the binding capacity with mitochondrial Prxs and the binding strength is different according to the existence of ROS, in vitro condition. Altogether, these results suggest that ROS dependent responses of CypD are related to mitochondrial Prxs.