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.

McDermott-Roe C., Ye J., Ahmed R., Sun X. M., Serafín A., Ware J., Bottolo L., Muckett P., Cañas X., Zhang J., et al.  (2011). Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function. Nature [Epub ahead of print] https://doi.org/10.1038/nature10490.
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Written by editorial staff. © 2011. Published by The Company of Biologists Ltd.
2011
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