Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

Wei Hua Lee, Hitoshi Higuchi, Sakae Ikeda, Erica L. Macke, Tetsuya Takimoto, Bikash R. Pattnaik, Che Liu, Li Fang Chu, Sandra M. Siepka, Kathleen J. Krentz, C. Dustin Rubinstein, Robert F. Kalejta, James A. Thomson, Robert F. Mullins, Joseph S. Takahashi, Lawrence H. Pinto, Akihiro Ikeda

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20 Citations (Scopus)

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.

Original languageEnglish
Article numbere19264
JournaleLife
Volume5
Issue numberNovember 2016
DOIs
Publication statusPublished - Nov 15 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Lee, W. H., Higuchi, H., Ikeda, S., Macke, E. L., Takimoto, T., Pattnaik, B. R., Liu, C., Chu, L. F., Siepka, S. M., Krentz, K. J., Rubinstein, C. D., Kalejta, R. F., Thomson, J. A., Mullins, R. F., Takahashi, J. S., Pinto, L. H., & Ikeda, A. (2016). Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies. eLife, 5(November 2016), [e19264]. https://doi.org/10.7554/eLife.19264