Format

Send to

Choose Destination
Free Radic Biol Med. 2015 Mar;80:84-92. doi: 10.1016/j.freeradbiomed.2014.12.018. Epub 2014 Dec 31.

IDH2 deficiency promotes mitochondrial dysfunction and cardiac hypertrophy in mice.

Author information

1
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Taegu, Korea.
2
Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, Korea.
3
Department of Food and Biotechnology, Korea University, Sejong, Korea.
4
Department of Anatomy, School of Medicine, Kyungpook National University, Taegu, Korea.
5
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Taegu, Korea. Electronic address: parkjw@knu.ac.kr.

Abstract

Cardiac hypertrophy, a risk factor for heart failure, is associated with enhanced oxidative stress in the mitochondria, resulting from high levels of reactive oxygen species (ROS). The balance between ROS generation and ROS detoxification dictates ROS levels. As such, disruption of these processes results in either increased or decreased levels of ROS. In previous publications, we have demonstrated that one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) is to control the mitochondrial redox balance, and thereby mediate the cellular defense against oxidative damage, via the production of NADPH. To explore the association between IDH2 expression and cardiac function, we measured myocardial hypertrophy, apoptosis, and contractile dysfunction in IDH2 knockout (idh2(-/-)) and wild-type (idh2(+/+)) mice. As expected, mitochondria from the hearts of knockout mice lacked IDH2 activity and the hearts of IDH2-deficient mice developed accelerated heart failure, increased levels of apoptosis and hypertrophy, and exhibited mitochondrial dysfunction, which was associated with a loss of redox homeostasis. Our results suggest that IDH2 plays an important role in maintaining both baseline mitochondrial function and cardiac contractile function following pressure-overload hypertrophy, by preventing oxidative stress.

KEYWORDS:

Apoptosis; Cardiac hypertrophy; IDH2; Mitochondria; Redox status

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center