A mouse model of creatine transporter deficiency syndrome: proteomic approach focused on mitochondrial proteins

Creatine (Cr) transporter deficiency syndrome-1 (CCDS1) is an X-linked metabolic disorder causing intellectual disability. Evidence of mitochondrial dysfunction in animal models of Cr deficiency suggests that mitochondrial function may also be abnormal. In this study we investigate the mitochondrial proteome in a CCDS1 mouse model to identify potential protein alterations. Mitochondria were obtained by differential centrifugation from brain of wild type (CrT +/y) and knock-out (CrT -/y) mice. Mitochondrial proteins extracts were separated by 2-DE and proteomic profiles compared by SameSpot. Fifty-nine spots resulted significantly differentially expressed in CrT -/y with respect to CrT +/y. Spots of interest were cut and analyzed by mass spectrometry. Identified proteins essentially appertained to mitochondrial respiratory chain and oxidative stress defense system. Ingenuity Pathways analysis was performed and the network generated involves free radical scavenging and neurological disease. Moreover, sirtuin and Nrf2 pathways resulted inhibited and activated, respectively. Overall our results suggest that CCDS1 activates the processes of ATP production and oxidative stress control.