TY - JOUR T1 - MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900308 VL - 2 IS - 4 SP - e201900308 AU - Shun Nagashima AU - Keisuke Takeda AU - Nobuhiko Ohno AU - Satoshi Ishido AU - Motohide Aoki AU - Yurika Saitoh AU - Takumi Takada AU - Takeshi Tokuyama AU - Ayumu Sugiura AU - Toshifumi Fukuda AU - Nobuko Matsushita AU - Ryoko Inatome AU - Shigeru Yanagi Y1 - 2019/08/01 UR - https://www.life-science-alliance.org/content/2/4/e201900308.abstract N2 - Mitochondrial abnormalities are associated with developmental disorders, although a causal relationship remains largely unknown. Here, we report that increased oxidative stress in neurons by deletion of mitochondrial ubiquitin ligase MITOL causes a potential neuroinflammation including aberrant astrogliosis and microglial activation, indicating that mitochondrial abnormalities might confer a risk for inflammatory diseases in brain such as psychiatric disorders. A role of MITOL in both mitochondrial dynamics and ER-mitochondria tethering prompted us to characterize three-dimensional structures of mitochondria in vivo. In MITOL-deficient neurons, we observed a significant reduction in the ER-mitochondria contact sites, which might lead to perturbation of phospholipids transfer, consequently reduce cardiolipin biogenesis. We also found that branched large mitochondria disappeared by deletion of MITOL. These morphological abnormalities of mitochondria resulted in enhanced oxidative stress in brain, which led to astrogliosis and microglial activation partly causing abnormal behavior. In conclusion, the reduced ER-mitochondria tethering and excessive mitochondrial fission may trigger neuroinflammation through oxidative stress. ER -