Dataset Information

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.

SUBMITTER: Lee WH

PROVIDER: S-EPMC5117855 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Mouse <i>Tmem135</i> mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies.

Lee Wei-Hua WH Higuchi Hitoshi H Ikeda Sakae S Macke Erica L EL Takimoto Tetsuya T Pattnaik Bikash R BR Liu Che C Chu Li-Fang LF Siepka Sandra M SM Krentz Kathleen J KJ Rubinstein C Dustin CD Kalejta Robert F RF Thomson James A JA Mullins Robert F RF Takahashi Joseph S JS Pinto Lawrence H LH Ikeda Akihiro A

eLife 20161115

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 (<i>Tmem135</i>) is responsible for these phenotypes. We observed l ...[more]

PMID: 27863209

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Dataset Information

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

Publications

Mouse <i>Tmem135</i> mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies.

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