Mitochondrial Lon protease controls ROS-dependent apoptosis in cardiomyocyte under hypoxia.
Apoptosis of cardiomyocytes, under ischemic conditions, has been identified as an essential process in the progression of heart failure. Under hypoxic conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). As ROS appear to have a critical role in heart failure, there has been considerable interest in identifying the candidate proteins involved and in developing strategies to reduce oxidative stress. Lon protease (Lon) is a multifunctional protein that mediates protein quality control and stress response in mitochondria. However, comprehensive and detailed studies, on the role of Lon in hypoxia-induced cardiomyocyte apoptosis, have yet to be carried out. In the present study, we demonstrated that hypoxia induced ROS-dependent cardiomyocyte apoptosis. Lon was upregulated in hypoxia-induced cardiomyocytes. Lon downregulation attenuated hypoxia-induced cardiomyocyte apoptosis through a reduction of ROS level. Moreover, overexpression of Lon stimulated ROS production and induced apoptosis under normoxic conditions in cardiomyocytes. Our results identify Lon as a novel regulator of cardiomyocyte fate and offers exciting new insights into the therapeutic potential of hypoxia-induced cardiomyocyte apoptosis.
Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
Chan-Yen
CY
Kuo
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
Yi-Chieh
YC
Chiu
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan. Electronic address: alanylee@nhri.org.tw.
Alan Yueh-Luen
AY
Lee
Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Cosmetic Science and Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan; Immunology Consortium, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan. Electronic address: htl@mail.cgu.edu.tw.
Tsong-Long
TL
Hwang
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D000860:Hypoxia; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000502:physiology*; D049070:Protease La / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D049070:Protease La
Apoptosis; Cardiomyocyte; Hypoxia; Mitochondrial Lon protease; Reactive oxygen species