Table 2.
The role of MFN2 in controlling inflammation, fibrosis, and atherogenesis
| Effects | Model | Mechanism | Ref |
|---|---|---|---|
| Inflammation | |||
| Inhibition of metabolic-induced inflammation | BMDMs from Mfn2-cKO mice | Enhancement of IL-12 secretion by ghrelin | [103] |
| Alleviation of blood-brain barrier breakdown | Cardiac ischemia/reperfusion injured rats | Increase in claudin5 by pretreatment of mitochondrial fusion promotor M1 | [16] |
| Suppression of LPS-induced mitochondrial dynamic disequilibrium | Murine NR8383 macrophage cells | Restoration of MFN1, MFN2, and OPA1 by activation of PKC-α/HO-1 signaling | [104] |
| Relieving mitochondrial dysfunction in nonalcoholic fatty liver disease and sepsis | BLN.CL2 hepatocytes; Human liver tissue; Trem2−/- mice | Decrease in a blockade MFN2 of miR-106b-5p through TREM2-mediated exosome | [105] |
| Fibrosis | |||
| Alleviation of liver fibrosis | AML12 hepatocytes; BMDMs; CCl4-induced liver fibrosis mice; HSC-T16 hepatic stellate cells | Suppression of TGF-β1/Smad signaling and collagen production | [106] |
| Protection from kidney fibrosis | Mfn2-cKO, PINK1−/-, Prkn−/- mice; BMDMs; Peritoneal macrophages; Renal macrophages | Enhancement of mitophagy through PINK1-mediated MFN2 phosphorylation and recruiting Parkin | [107] |
| Atherogenesis | |||
| Inhibition of intracellular lipid accumulation | ApoE−/- mice; RAW264.7 and THP-1 cells | Induction of cholesterol transporters by PPARγ activation and inhibition of ERK1/2 and p38 | [108] |
| Augmentation of mitophagy in oxidized LDL-exposed status | Apoa1bp−/- mice; BMDMs; HEK 293T cells; Human carotid tissue | Ubiquitination of MFN2 through interaction between Parkin and N-terminal domain of AIBP | [17] |
AIBP, apolipoprotein A-I binding protein (encoded by Apoa1bp gene); ApoE, apolipoprotein E; BMDM, bone marrow-derived macrophage; ERK1/2, extracellular signal-regulated protein kinase 1/2; HO-1, heme oxygenase-1; IL-12, interleukin 12; LDL, low-density lipoprotein; LPS, lipopolysaccharides; MFN2, mitofusin2; Mfn2-cKO mice, Mfn2fl/fl:LysMc/c conditional knock-out mice; OPA1, optic atrophy 1 (mitochondrial dynamin like GTPase); PINK1, phosphatase and tensin homolog-induced kinase 1; PKC-α, protein kinase C-alpha; PPARγ, peroxisome proliferator-activated receptor gamma; TGF-β1, transforming growth factor beta 1; TREM2, triggering receptor expressed on myeloid cells 2