TY - JOUR TI - Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling AU - Kim, Young-Mee AU - Krantz, Sarah AU - Jambusaria, Ankit AU - Toth, Peter T. AU - Moon, Hyung-Geun AU - Gunarathna, Isuru AU - Park, Gye Young AU - Rehman, Jalees T2 - Nature Communications AB - Endothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of vascular endothelial (VE)-cadherin as well as accessory proteins such as β-catenin and p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and β-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/β-catenin complex disassociates from the AJs and Mfn2 accumulates in the nucleus where Mfn2 negatively regulates the transcriptional activity of β-catenin. Endothelial-specific deletion of Mfn2 results in inflammatory activation, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non-canonical manner to suppress the inflammatory response by stabilizing cell–cell adherens junctions and by binding to the transcriptional activator β-catenin. DA - 2021/05/12/ PY - 2021 DO - 10.1038/s41467-021-23047-6 DP - www.nature.com VL - 12 IS - 1 SP - 2736 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-23047-6 Y2 - 2021/05/12/23:06:31 ER -