ABSTRACT
Remodeling of the mitochondrial network is an important process in the maintenance of cellular homeostasis and is closely related to mitochondrial function. Interactions between the biogenesis of new mitochondria and the clearance of damaged mitochondria (mitophagy) is an important manifestation of mitochondrial network remodeling. Mitochondrial fission and fusion act as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been described in a variety of tissues and cell types and under a variety of conditions. For example, robust remodeling of the mitochondrial network has been reported during the polarization and effector function of macrophages. Previous studies have also revealed the important role of mitochondrial morphological structure and metabolic changes in regulating the function of macrophages. Therefore, the processes that regulate remodeling of the mitochondrial network also play a crucial role in the immune response of macrophages. In this paper, we focus on the molecular mechanisms of mitochondrial regeneration, fission, fusion, and mitophagy in the process of mitochondrial network remodeling, and integrate these mechanisms to investigate their biological roles in macrophage polarization, inflammasome activation, and efferocytosis.
Subject(s)
Mitochondria , Mitophagy , Homeostasis/physiology , Phagocytosis , Macrophages/metabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the role of toll-like receptor 4 (TLR4) on oxidized low-density/β₂-glycoprotein I/β₂-glycoprotein I (ox-LDL/β₂GPI/anti-β₂GPI) antibodies complex induced macrophage foam cell formation.</p><p><b>METHODS</b>The peritoneal macrophages were separated from TLR4 intact C3H/HeN mice and TLR4 defective C3H/HeJ mice. The cells were treated with ox-LDL, ox-LDL/β₂GPI, ox-LDL/anti-β₂GPI, anti-β₂GPI/β₂GPI, ox-LDL/β₂GPI/anti-β₂GPI, lipopolysaccharide (LPS) for 48 h and the foam cells were identified by Oil red O staining for intracellular lipids. The total cellular RNA and the protein lysates were collected. The levels of tissue factor (TF) mRNA in two groups were detected by real-time PCR (RT-PCR), and the expression of phosphorylated nuclear factor-κB (NF-κB) p65 was detected by Western blotting. Monocyte chemotactic protein-1 (MCP-1) secretion from peritoneal macrophages was determined by enzyme linked immunosorbent assay (ELISA) kits.</p><p><b>RESULTS</b>Compared with C3H/HeJ mice, lipid droplets in the cytoplasm of peritoneal macrophages from C3H/HeN mice were significantly increased and phosphorylation-NF-κB expression was significantly upregulated after stimulating by ox-LDL/β₂GPI/anti-β₂GPI complex (P < 0.01). TF mRNA and MCP-1 expression were also upregulated post ox-LDL/β₂GPI/anti-β₂GPI complex stimulation [TF mRNA: 0.041 ± 0.023 vs. 0.005 ± 0.003; MCP-1: (6 200.2 ± 6.4) pg/ml vs. (803.3 ± 5.5) pg/ml, P < 0.01].</p><p><b>CONCLUSION</b>TLR4 can enhance ox-LDL/β₂GPI/anti-β₂GPI complex induced peritoneal macrophage foam cell formation via upregulating phosphorylation-NF-κB, TF and MCP-1 expression.</p>