Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies
- University of Wisconsin-Madison, United States
- Okayama University Hospital, Japan
- Morgridge Institute for Research, United States
- Northwestern University, United States
- University of Iowa, United States
- Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States
Abstract
While 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.
Article and author information
Author details
Joseph S Takahashi
Funding
National Institutes of Health (R21 EY023061, R01 EY022086)
- Akihiro Ikeda
Retina Research Foundation (Professorship)
- Akihiro Ikeda
Howard Hughes Medical Institute
- Joseph S Takahashi
National Institutes of Health (U01 MH61915)
- Joseph S Takahashi
National Institutes of Health (P30 845 EY016665, P30 HD003352)
- Akihiro Ikeda
National Institutes of Health (T32 GM007133)
- Erica L Macke
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeremy Nathans, Johns Hopkins University School of Medicine, United States
Ethics
Animal experimentation: All experiments were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee (IACUC) protocols (M01771) at the University of Wisconsin-Madison.
Version history
- Received: July 1, 2016
- Accepted: October 25, 2016
- Accepted Manuscript published: November 15, 2016 (version 1)
- Version of Record published: November 21, 2016 (version 2)
Copyright
© 2016, Lee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies
eLife 5:e19264.
https://doi.org/10.7554/eLife.19264
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