期刊
LIFE SCIENCE ALLIANCE
卷 2, 期 4, 页码 -出版社
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.201900308
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资金
- MEXT/JSPS KAKENHI
- MEXT
- JSPS KAKENHI
- Comprehensive Brain Science Network (CBSN)
- National Institute for Physiological Sciences
- National Center of Neurology and Psychiatry [30-5]
- Uehara Memorial Foundation
- Naito Foundation
- Sumitomo Science Foundation
- Cosmetology Research Foundation
- Ono Medical Research Foundation
- Tokyo Biochemical Research Foundation
- AMED [JP17gm5010002, JP18gm5010002]
- Grants-in-Aid for Scientific Research [19K16527] Funding Source: KAKEN
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.
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