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

Research output: Contribution to journalArticle

10 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

Fingerprint

Mitochondrial Dynamics
Pathology
Aging of materials
Mutation
Retina
Retinal Diseases
Conservation of Natural Resources
Mitochondria
Oxidative Stress
Oxidative stress
Phenotype
Fusion reactions
Genes

ASJC Scopus subject areas

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

Cite this

Lee, W. H., Higuchi, H., Ikeda, S., Macke, E. L., Takimoto, T., Pattnaik, B. R., ... 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

Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies. / Lee, Wei Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L.; Takimoto, Tetsuya; Pattnaik, Bikash R.; Liu, Che; Chu, Li Fang; Siepka, Sandra M.; Krentz, Kathleen J.; Rubinstein, C. Dustin; Kalejta, Robert F.; Thomson, James A.; Mullins, Robert F.; Takahashi, Joseph S.; Pinto, Lawrence H.; Ikeda, Akihiro.

In: eLife, Vol. 5, No. November 2016, e19264, 15.11.2016.

Research output: Contribution to journalArticle

Lee, WH, Higuchi, H, Ikeda, S, Macke, EL, Takimoto, T, Pattnaik, BR, Liu, C, Chu, LF, Siepka, SM, Krentz, KJ, Rubinstein, CD, Kalejta, RF, Thomson, JA, Mullins, RF, Takahashi, JS, Pinto, LH & Ikeda, A 2016, 'Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies', eLife, vol. 5, no. November 2016, e19264. https://doi.org/10.7554/eLife.19264
Lee, Wei Hua ; Higuchi, Hitoshi ; Ikeda, Sakae ; Macke, Erica L. ; Takimoto, Tetsuya ; Pattnaik, Bikash R. ; Liu, Che ; Chu, Li Fang ; Siepka, Sandra M. ; Krentz, Kathleen J. ; Rubinstein, C. Dustin ; Kalejta, Robert F. ; Thomson, James A. ; Mullins, Robert F. ; Takahashi, Joseph S. ; Pinto, Lawrence H. ; Ikeda, Akihiro. / Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies. In: eLife. 2016 ; Vol. 5, No. November 2016.
@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",
year = "2016",
month = "11",
day = "15",
doi = "10.7554/eLife.19264",
language = "English",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "November 2016",

}

TY - JOUR

T1 - Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

AU - Lee, Wei Hua

AU - Higuchi, Hitoshi

AU - Ikeda, Sakae

AU - Macke, Erica L.

AU - Takimoto, Tetsuya

AU - Pattnaik, Bikash R.

AU - Liu, Che

AU - Chu, Li Fang

AU - Siepka, Sandra M.

AU - Krentz, Kathleen J.

AU - Rubinstein, C. Dustin

AU - Kalejta, Robert F.

AU - Thomson, James A.

AU - Mullins, Robert F.

AU - Takahashi, Joseph S.

AU - Pinto, Lawrence H.

AU - Ikeda, Akihiro

PY - 2016/11/15

Y1 - 2016/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84997079862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84997079862&partnerID=8YFLogxK

U2 - 10.7554/eLife.19264

DO - 10.7554/eLife.19264

M3 - Article

C2 - 27863209

AN - SCOPUS:84997079862

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

IS - November 2016

M1 - e19264

ER -