The effect of Tmem135 overexpression on the mouse heart

Sarah Aileen Lewis, Tetsuya Takimoto, Shima Mehrvar, Hitoshi Higuchi, Anna Lisa Doebley, Giangela Stokes, Nader Sheibani, Sakae Ikeda, Mahsa Ranji, Akihiro Ikeda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Tissues with high-energy demand including the heart are rich in the energy-producing organelles, mitochondria, and sensitive to mitochondrial dysfunction. While alterations in mitochondrial function are increasingly recognized in cardiovascular diseases, the molecular mechanisms through which changes in mitochondria lead to heart abnormalities have not been fully elucidated. Here, we report that transgenic mice overexpressing a novel regulator of mitochondrial dynamics, transmembrane protein 135 (Tmem135), exhibit increased fragmentation of mitochondria and disease phenotypes in the heart including collagen accumulation and hypertrophy. The gene expression analysis showed that genes associated with ER stress and unfolded protein response, and especially the pathway involving activating transcription factor 4, are upregulated in the heart of Tmem135 transgenic mice. It also showed that gene expression changes in the heart of Tmem135 transgenic mice significantly overlap with those of aged mice in addition to the similarity in cardiac phenotypes, suggesting that changes in mitochondrial dynamics may be involved in the development of heart abnormalities associated with aging. Our study revealed the pathological consequence of overexpression of Tmem135, and suggested downstream molecular changes that may underlie those disease pathologies.

Original languageEnglish
Article numbere0201986
JournalPloS one
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Lewis, S. A., Takimoto, T., Mehrvar, S., Higuchi, H., Doebley, A. L., Stokes, G., Sheibani, N., Ikeda, S., Ranji, M., & Ikeda, A. (2018). The effect of Tmem135 overexpression on the mouse heart. PloS one, 13(8), [e0201986]. https://doi.org/10.1371/journal.pone.0201986