Mitofusin 2 Promotes Apoptosis of CD4+ T Cells by Inhibiting Autophagy in Sepsis

• Published in: Mediators of inflammation Vol. 2017; no. 2017; pp. 1 - 15
• Main Authors: Lu, Zhongqiu, Yao, Yong-Ming, Dong, Ning, Zhang, Hui, Hong, Guang-Liang, Ke, He-Liang, Wu, You, Zhao, Guang-Ju, Ying, Lan, Wu, Yao
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2017; Hindawi; Hindawi Limited
• Subjects: 12-O-Tetradecanoylphorbol-13-acetate; Acetic acid; Animals; Apoptosis; Autophagy; Autophagy - physiology; Cardiomyocytes; CD4 antigen; CD4-Positive T-Lymphocytes - physiology; Cecum; Emergency medical care; Endoplasmic reticulum; GTP Phosphohydrolases - physiology; Humans; Immunoglobulins; Ionomycin; Jurkat Cells; Kidneys; Laboratory animals; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Male; Medical research; Membrane proteins; Mice; Mice, Inbred BALB C; Microtubule-Associated Proteins - physiology; Mitochondria; Phagocytosis; Physiology; Proteins; Rapamycin; Rodents; Sepsis; Sepsis - immunology; Spleen; Studies; China
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2017/4926205

Apoptosis of CD4+ T cells is a primary pathophysiological mechanism of immune dysfunction in the pathogenesis of sepsis. Mitofusin 2 (Mfn2), an integral mitochondrial outer membrane protein, has been confirmed to be associated with cellular metabolism, proliferation, and apoptosis. The function of Mfn2 in CD4+ T cell apoptosis in sepsis is poorly understood. Here, we discovered increased in vivo Mfn2 expression, autophagy deficiency, and elevated cell apoptosis in murine splenic CD4+ T cells after cecal ligation and puncture (CLP). We also observed almost identical results in splenic CD4+ T cells upon lipopolysaccharide (LPS) stimulation in vitro. Furthermore, overexpression of Mfn2 resulted in impaired autophagy and increased apoptosis in Jurkat cells. Pharmacological inhibition of autophagy with 3-methyladenine enhanced Mfn2 overexpression-induced cell apoptosis. In addition, overexpression of Mfn2 downregulated phorbol myristate acetate (PMA)/ionomycin-, rapamycin- and starvation-induced autophagy in Jurkat T cells. Taken together, these data indicate a critical role of Mfn2 in CD4+ T cell apoptosis in sepsis and the underlying mechanism of autophagy deficiency.