TY - JOUR
T1 - The effect of Tmem135 overexpression on the mouse heart
AU - Lewis, Sarah Aileen
AU - Takimoto, Tetsuya
AU - Mehrvar, Shima
AU - Higuchi, Hitoshi
AU - Doebley, Anna Lisa
AU - Stokes, Giangela
AU - Sheibani, Nader
AU - Ikeda, Sakae
AU - Ranji, Mahsa
AU - Ikeda, Akihiro
N1 - Funding Information:
The research herein was funded by the National Institutes of Health (NIH) (R01 EY022086; https://www.nih.gov/) to AI, a research agreement with Ajinomoto Co., Inc. (https://www.ajinomoto. com/en/) to AI, a professorship from the Retina Research Foundation (Walter H. Helmerich Research Chair; https://retinaresearchfnd.org/) to AI, the Timothy William Trout Professorship in Eye Research to AI, the National Eye Institute Core Grant for Vision Research (P30 EY016665; https://nei.nih.gov/), a National Science Foundation Graduate Research Fellowship (grant No. 403-4030513; https://www.nsfgrfp.org/) to SAL, UWM Research Growth Initiative (RGI) 101x290 to MR (http://uwm.edu/), an unrestricted award from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences (https://www.rpbusa.org/), NIH (EY026078; https://www.nih.gov/) to NS, Retina Research Foundation (https://retinaresearchfnd.org/) to NS, Environmental Protection Agency (EPA) (83573701; https://www.epa.gov/) to NS, and Stein RPB Innovation Award to NS (https://www.rpbusa.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Additionally, Ajinomoto Co., Inc., provided support in the form of salary for an author [TT], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of authors are articulated in the ‘author contributions’ section.
Publisher Copyright:
© 2018 Lewis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0201986
DO - 10.1371/journal.pone.0201986
M3 - Article
C2 - 30102730
AN - SCOPUS:85051472598
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 8
M1 - e0201986
ER -
