Mouse Mutation Reveals a Mechanism Involving Mitochondrial Dynamics That Leads to Age-dependent Retinal Pathologies

Overview

Journal Elife

Specialty Biology

Date 2016 Nov 19

PMID 27863209

Citations 32

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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TMEM135 deficiency improves hepatic steatosis by suppressing CD36 in a SIRT1-dependent manner.

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Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes.

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Roles of transmembrane protein 135 in mitochondrial and peroxisomal functions - implications for age-related retinal disease.

Landowski M, Gogoi P, Ikeda S, Ikeda A Front Ophthalmol (Lausanne). 2024; 4.

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