High left ventricular mass (LVM) is a heritable risk factor for heart failure and sudden death, but its genetic regulators are not well defined. McDermott-Roe et al. used several rat models to identify that reduced expression of endonuclease G (Endog) is associated with a blood-pressure-independent increase in cardiac mass. In vitro, reduced Endog expression caused cardiomyocyte hypertrophy as well as increased levels of mitochondrial reactive oxygen species, a signal known to promote hypertrophy. In line with these findings, Endog−/− mice were found to exhibit mitochondrial dysfunction and depletion, cardiac hypertrophy, and cardiac steatosis. Analysis of human cardiac expression data located ENDOG within a mitochondrial gene network, and further experiments showed that ENDOG is regulated by PCG1α and ERRα, two key transcription factors for mitochondrial and heart function. Finally, the authors show that ENDOG binds directly to mitochondrial DNA and seems to regulate mitochondrial biogenesis. These data define ENDOG as a regulator of mitochondrial function and might help to define the molecular mechanisms underlying blood-pressure-independent cardiac hypertrophy in humans.
- Written by editorial staff. © 2011. Published by The Company of Biologists Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
Featured article - Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping
This Research article from Bryan C. Bjork and co-workers describes the first targeting of an invertible gene trap to generate a conditional Prdm16 mouse allele and its use to assess phenotypic consequences of Prdm16 loss during craniofacial and brain development.
Review - Cell models of arrhythmogenic cardiomyopathy: advances and opportunities
Elena Sommariva and colleagues reappraise past discoveries in in vitro models of arrhythmogenic cardiomyopathy (ACM) in this Review, providing insights into the molecular mechanisms of this disease.
Editor’s choice - Small-molecule therapeutic boosts spatial memory and motor function in Rett syndrome mice
Rett syndrome is caused by a mutation triggering decreased levels of protein BDNF. Small-molecule BDNF mimetic, LM22A-4, has previously been shown to improve respiratory problems associated with the disease. Now, new research from Lucas Pozzo-Miller and colleagues reveals that LM22A-4 may also improve spatial memory and motor skill defects in a Rett syndrome mouse model. Read the Research article here, and the press release here.
Featured article - Imaging of viral neuroinvasion in the zebrafish reveals that Sindbis and chikungunya viruses favour different entry routes
In this Research article from Gabriella Passoni and co-workers, imaging of neuroinvasion in zebrafish shows that chikungunya virus first infects the blood-brain barrier, whereas Sindbis virus relies on axonal transport.
Why should you publish your next paper in Disease Models & Mechanisms?
From single-celled organisms to patient-derived models, cancer to neurodegeneration, Disease Models & Mechanisms publishes the best original research and resources that focus on the use of model systems to better understand, diagnose and treat human disease. Submit your paper here.
Transfer to Biology Open
If your submission to Disease Models & Mechanisms is unsuccessful, did you know you can transfer your paper and any reviews directly to our sister journal, Biology Open? The majority of papers transferred with reviews are accepted for publication. Find out how here.