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

doi:10.7554/eLife.19264

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

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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, …

eLife, Vol.5(November 2016), e19264

11/15/2016

DOI: 10.7554/eLife.19264

PMCID: PMC5117855

PMID: 27863209

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https://doi.org/10.7554/eLife.19264View

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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 ( ) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant as well as 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.

Aging

Mitochondrial Dynamics

Adaptor Proteins, Signal Transducing - analysis

Animals

Nuclear Proteins - analysis

Adaptor Proteins, Signal Transducing - genetics

Mutant Proteins - genetics

Retinal Diseases - pathology

Mice

Mitochondria - chemistry

Mutant Proteins - analysis

Nuclear Proteins - genetics

Details

Title: Subtitle: Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies
Creators: Wei-Hua Lee - Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States
Hitoshi Higuchi - Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States
Sakae Ikeda - McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, United States
Erica L Macke - Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States
Tetsuya Takimoto - Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States
Bikash R Pattnaik - Department of Pediatrics, University of Wisconsin-Madison, Madison, United States
Che Liu - University of Wisconsin–Madison
Li-Fang Chu - Morgridge Institute for Research, Madison, United States
Sandra M Siepka - Department of Neurobiology, Northwestern University, Evanston, United States
Kathleen J Krentz - Transgenic Mouse Facility, Biotechnology Center, University of Wisconsin-Madison, Madison, United States
C Dustin Rubinstein - Translational Genomics Facility, Biotechnology Center, University of Wisconsin-Madison, Madison, United States
Robert F Kalejta - McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, United States
James A Thomson - Morgridge Institute for Research, Madison, United States
Robert F Mullins - Department of Ophthalmology and Visual, University of Iowa, Iowa City, United States
Joseph S Takahashi - Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
Lawrence H Pinto - Department of Neurobiology, Northwestern University, Evanston, United States
Akihiro Ikeda - McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, United States
Resource Type: Journal article
Publication Details: eLife, Vol.5(November 2016), e19264
DOI: 10.7554/eLife.19264
PMID: 27863209
PMCID: PMC5117855
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: England
Grant note: P30 EY016665 / NEI NIH HHS Howard Hughes Medical Institute R21 EY023061 / NEI NIH HHS P30 HD003352 / NICHD NIH HHS R01 EY022086 / NEI NIH HHS U01 MH061915 / NIMH NIH HHS T32 GM007133 / NIGMS NIH HHS
Language: English
Date published: 11/15/2016
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983979953102771

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