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Dr. Jun Zhang's research focuses on free radicals produced by mitochondrial activity can damage cellular components and macromolecules, including lipids, proteins and DNA, leading to aging. Cardiolipin is a mitochondrial membrane phospholipid required for oxidative phosphorylation and mitochondrial biogenesis. In contrast to other phospholipids, the biological function of cardiolipin is determined by its acyl composition, which is dominated by linoleic acid in healthy metabolic tissues, such as heart, liver, and skeletal muscle. Oxidized cardiolipin serves as a new source of ROS, initiating a chain of events of oxidative stress and CL oxidation known as “CL peroxidation” which is implicated in the mitochondrial dysfunction of aging and age-related diseases. Our research work focuses on the molecular mechanisms of pathological cardiolipin remodeling and mitochondrial dysfunction in aging and the onset of aging-related diseases, including diabetes, obesity, cardiovascular diseases and neurodegenerative diseases. We are also uncovering the molecular regulation roles of mitochondrial function and mitochondrial phospholipids in several cellular processes, including autophagy, apoptosis, inflammation and innate immune response.
1. Jun Zhang*, John-Paul Andersen, Haoran Sun, Xuyun Liu, Nahum Sonenberg, Jia Nie, and Yuguang Shi. Aster-C Coordinates with COP I Vesicles to Regulate Lysosomal Trafficking and Activation of mTORC1. EMBO Reports, 2020; e49898.
2. John-Paul Andersen, Jun Zhang*, Haoran Sun, Xuyun Liu, Jiankang Liu, Jia Nie, and Yuguang Shi. Aster-B Coordinates with Arf1 to Regulate Mitochondrial Cholesterol Transport. Molecular Metabolism, 2020; 101055.
3. Chengjie Song, Jun Zhang, Shasha Qi, Zhen Liu, Xiaoyang Zhang, Yue Zheng, John-Paul Andersen, Weiping Zhang, Randy Strong, Paul Anthony Martinez, Nicolas Musi, Jia Nie, and Yuguang Shi. Cardiolipin Remodeling by ALCAT1 Links Mitochondrial Dysfunction to Parkinson’s Diseases. Aging Cell, 2019;e12941.
4. Xiaoyang Zhang, Jun Zhang*, Haoran Sun, Xueling Liu, Yue Zheng, Dan Xu, Jianing Wang, Dandan Jia, Xianlin Han, Feng Liu, Jia Nie, and Yuguang Shi. (2019). Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to Hepatosteatosis. Cellular and Molecular Gastroenterology and Hepatology, 2019;7:763–781.
5. Jing Wang, Pengfei Xu, Xinni Xie, Jiao Li, Jun Zhang, Jialin Wang, Fan Hong, Jian Li, Youyi Zhang, Yao Song, Xiaohui Zheng, and Yonggong Zhai. DBZ (Danshensu Bingpian Zhi), a Novel Natural Compound Derivative, Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice. J Am Heart Assoc, 2017, 6(10): e006297.
6. Pengfei Xu, Shu Dai, Jing Wang, Jun Zhang, Jin Liu, Fang Wang, and Yonggong Zhai. Preventive Obesity Agent Montmorillonite Adsorbs Dietary Lipids and Enhances Lipid Excretion from the Digestive Tract. Scientific Report, 2016, 6: 19659 | DOI: 10.1038/srep19659.
7. Ying Liu, Yoshinori Takahashi, Neelam Desai, Jun Zhang, Jacob M. Serfass, Yu-Guang Shi, Christopher J. Lynch, and Hong-Gang Wang. Bif-1 Deficiency Impairs Lipid Homeostasis and Causes Obesity Accompanied by Insulin Resistance. Scientific Report, 2016, 6:20453 | DOI: 10.1038/srep20453.
8. Paul Hsu, Xiaolei Liu, Jun Zhang, Hong-Gang Wang, Ji-Ming Ye, and Yuguang Shi. Cardiolipin Remodeling by TAZ/tafazzin is Selectively Required for the Initiation of Mitophagy. Autophagy, 2015, 11(4):643-52.
9．Li Wang, Xiaolei Liu, Jia Nie, Jun Zhang, Scot R. Kimball, Hai Zhang, Weiping J. Zhang, Leonard S. Jefferson, Zeneng Cheng, Qiuhe Ji, and Yuguang Shi. ALCAT1 Controls Mitochondrial Etiology of Fatty Liver Diseases, Linking Defective Mitophagy to Hepatosteatosis. Hepatology, 2015, 61(2):486-96.
10. Jun Zhang*, Dan Xu, Jia Nie, Ruili Han, Yonggong Zhai, and Yuguang Shi. Comparative Gene Identification-58 (CGI-58) Promotes Autophagy as a Putative Lysophosphatidylglycerol Acyltransferase. Journal of Biological Chemistry, 2014, 289(47):33044-53.
11. Jun Zhang*, Dan Xu, Jia Nie, Jingsong Cao, Yonggong Zhai, Dewen Tong and Yuguang Shi. Monoacylglycerol Acyltransferase-2 Is a Tetrameric Enzyme That Selectively Heterodimerizes with Diacylglycerol Acyltransferase-1. Journal of Biological Chemistry, 2014, 289:10909-10918.
12. Jia Nie, Xiaolei Liu, Brendan N. Lilley, Hai Zhang, Y. Albert Pan, Scot R. Kimball, Jun Zhang, Weiping Zhang, Li Wang, Leonard S. Jefferson, Joshua R. Sanes, Xiao Hana, and Yuguang Shi. SAD-A Kinase Controls Islet β-cell Size and Function as a Mediator of mTORC1 Signaling. Proc Natl Acad Sci USA, 2013, 110(34): 13857-62.
13. Jun Zhang*, Yijuan Wei, Bingfang Hu, Min Huang, Wen Xie, Yonggong Zhai. Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells. Plos One, 2013, 8(7): e67959.
14. Xinni Xie, Shixiang Wang, Lei Xiao, Jun Zhang, Jing Wang, Jin Liu, Xuji Shen, Dacheng He, Xiaohui Zheng and Yonggong Zhai. DBZ Blocks LPS-induced Monocyte Activation and Foam Cell Formation via Inhibiting Nuclear Factor-κB. Cellular Physiology and Biochemistry, 2011, 28:649-662.
15. Lei Xiao, Jun Zhang, Hongxing Li, Jin Liu, Lan He, Junjie Zhang and Yonggong Zhai. Inhibition of Adipocyte Differentiation and Adipogenesis by the Traditional Chinese Herb Sibiraea Angustata. Experimental Biology and Medicine, 2010, 235:1442-1449.