Novel role of mitochondrial GTPases 1 in pathological cardiac hypertrophy

Dachun Xu, Yifan Zhao, Xinyu Weng, Yuyan Lu, Weiming Li, Kai Tang, Wei Chen, Zheng Liu, Xinrui Qi, Jialing Zheng, John Fassett, Yi Zhang, Yawei Xu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


While most mitochondrial proteins are encoded in the nucleus and translated on cytosolic/endoplasmic reticulum ribosomes, proteins encoded by mitochondrial DNA are translated on mitochondrial ribosomes. Mitochondrial GTPases 1 (MTG1) regulates mitochondrial ribosome assembly and translation, but its impact on cardiac adaptation to stress is unknown. Here, we found that MTG1 is dramatically elevated in hearts of dilated cardiomyopathy patients and in mice exposed to left ventricular pressure overload (AB). To examine the role of MTG1 in cardiac hypertrophy and heart failure, MTG1 loss/gain of function studies were performed in cultured cardiomyocytes and mice exposed to hypertrophic stress. MTG1 shRNA and adenoviral overexpression studies indicated that MTG1 expression attenuates angiotensin II-induced hypertrophy in cultured cardiomyocytes, while MTG1 KO mice exhibited no observable cardiac phenotype under basal conditions. MTG1 deficiency significantly exacerbated AB-induced cardiac hypertrophy, expression of hypertrophic stress markers, fibrosis, and LV dysfunction in comparison to WT mice. Conversely, transgenic cardiac MTG1 expression attenuated AB-induced hypertrophy and LV dysfunction. Mechanistically, MTG1 preserved mitochondrial respiratory chain complex activity during pressure overload, which further attenuated ROS generation. Moreover, we demonstrated that TAK1, P38 and JNK1/2 activity is downregulated in the MTG1 overexpression group. Importantly, dampening oxidative stress with N-acetylcysteine (NAC) lowered hypertrophy in MTG1 KO to WT levels. Collectively, our data indicate that MTG1 protects against pressure overload-induced cardiac hypertrophy and dysfunction by preserving mitochondrial function and reducing oxidative stress and downstream TAK1 stress signaling.

Original languageEnglish (US)
Pages (from-to)105-116
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
StatePublished - Mar 2019

Bibliographical note

Funding Information:
We would like to thank Hongliang Li from the Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University and Yingjie chen from the Cardiovascular Division and Lillehei Heart Institute, University of Minnesota for their help with study design and helpful discussions. This work has been supported by grants from National Natural Science Foundation of China (No. 81270194 , 81770391 to Dachun Xu; No. 81470394 , 81770226 to Yawei Xu and No. 81700210 to Yifan Zhao), also sponsored by Shanghai Sailing Program (No. 17YF1414800 ).

Publisher Copyright:
© 2019


  • Cardiac hypertrophy
  • MAPK
  • Mitochondrial GTPases 1
  • Oxidative stress
  • TAK1

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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