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Cited by 52Mitochondrial Function and PathologyRetinal Development and DisordersGenetics, Aging, and Longevity in Model Organisms

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

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Lee, Wei-Hua, Higuchi, Hitoshi, Ikeda, Sakae, Macke, Erica L, Takimoto, Tetsuya, Pattnaik, Bikash R, Liu, Che, Chu, Li-Fang +9 more·2016·eLife
DOI 10.7554/elife.19264PMC PMC5117855
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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 (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.

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  • Loss of CG31259 (TMEM135) causes mitochondrial defects.

    “with loss of CG31259 (TMEM135) causing mitochondrial defects”

    From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [69]

    The Results sections on mitochondrial dynamics and metabolism report abnormal mitochondrial networks and reduced respiration in mouse cells carrying a Tmem135 mutation. But the paper studies a truncated mutant protein, not loss of CG31259; it does not establish the claim for CG31259 specifically. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Nothing has been reported for CG3223 (UBL7).

    “nothing reported for CG3223 (UBL7) [69,70].”

    From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [69]

    The Materials and methods passages describe mouse Tmem135 experiments, and the Discussion passage returned by the search concerns TMEM135 and mitochondrial fission. Searches for CG3223, UBL7, and ubiquitin-like protein 7 found no passage addressing whether anything has been reported for CG3223 (UBL7). (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Lee, W.-H., Higuchi, H., Ikeda, S., Macke, E. L., Takimoto, T., Pattnaik, B. R., Liu, C., Chu, L.-F., Siepka, S. M., Krentz, K. J., Rubinstein, C. D., Kalejta, R. F., Thomson, J. A., Mullins, R. F., Takahashi, J. S., Pinto, L. H., & Ikeda, A.
Affiliations
  • Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States
  • University of Wisconsin–Madison (US)
  • Morgridge Institute for Research (US)
  • Northwestern University (US)
  • University of Iowa (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Ikeda, Akihiro
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2016-11-15
Volume
5
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.19264
PMC
PMC5117855
OpenAlex
W2553083157
Cited by
52
References
5
Citations by year
2026: 4 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 3
FWCI
2.43
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (T32 GM007133, U01 MH61915, R21 EY023061, P30 845 EY016665, P30 HD003352, R01 EY022086)
  • Howard Hughes Medical Institute
  • Retina Research Foundation (Professorship)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
retinal aging, mitochondrial dynamics, mitochondrial fission, mitochondrial fusion, oxidative stress sensitivity, mouse mutants, retinal mitochondria
MeSH terms
Aging, Animals, Mitochondria, Nuclear Proteins, Retinal Diseases, Adaptor Proteins, Signal Transducing, Mutant Proteins, Mice, Mitochondrial Dynamics

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