@article{3c0aaf3c914e446db1783d144d04a15d,
title = "Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies",
abstract = "While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases.",
author = "Lee, {Wei Hua} and Hitoshi Higuchi and Sakae Ikeda and Macke, {Erica L.} and Tetsuya Takimoto and Pattnaik, {Bikash R.} and Che Liu and Chu, {Li Fang} and Siepka, {Sandra M.} and Krentz, {Kathleen J.} and Rubinstein, {C. Dustin} and Kalejta, {Robert F.} and Thomson, {James A.} and Mullins, {Robert F.} and Takahashi, {Joseph S.} and Pinto, {Lawrence H.} and Akihiro Ikeda",
note = "Funding Information: We thank Satoshi Kinoshita for generation of frozen sections, Drs. Aparna Lakkaraju and Kimberly A Toops for the advice on live imaging experiments, and Drs. David Gamm, Aparna Lakkaraju, and Shigemi Matsuyama as well as Sarah Lewis for comments on the manuscript. The pX330-U6-Chimeric plasmid was a gift from Feng Zhang (Addgene plasmid # 42230). This work was supported by Grants from the National Institutes of Health (NIH R21 EY023061 and R01 EY022086) and a professorship from the Retina Research Foundation (Walter H. Helmerich Research Chair) to AI, NIH grant U01 MH61915 to JST, Core Grant for Vision Research (P30 EY016665) and a Core Grant to Waisman Center (NIH P30 HD003352). JST is an Investigator in the Howard Hughes Medical Institute. Support for ELM was partially provided by the NIH predoctoral training program in Genetics (NIH T32 GM007133). Publisher Copyright: {\textcopyright} Lee et al.",
year = "2016",
month = nov,
day = "15",
doi = "10.7554/eLife.19264",
language = "English",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "November 2016",
}