Interestingly, an adjacent human mutation, R340H, in the ND4 gene also results in CID with associated LS, Leber hereditary optic neuropathy and late onset MELAS syndrome, characterized by increased ROS production and altered CI assembly (Wong et al., 2002; Deschauer et al., 2003), prompting a new investigative field for the development of therapeutic approaches targeting mitochondria for the treatment of AD and CID (Friedland-Leuner et al., 2014). Here, MT-ND4 is linked to MELAS.