TY  - JOUR
A1  - Khodzhaeva, Vera
A1  - Schreiber, Yannick
A1  - Geisslinger, Gerd
A1  - Brandes, Ralf
A1  - Brüne, Bernhard
A1  - Namgaladze, Dmitry
T1  - Mitofusin 2 deficiency causes pro-inflammatory effects in human primary macrophages
T2  - Frontiers in immunology
N2  - Mitofusin 2 (MFN2) is a mitochondrial outer membrane GTPase, which modulates mitochondrial fusion and affects the interaction between endoplasmic reticulum and mitochondria. Here, we explored how MFN2 influences mitochondrial functions and inflammatory responses towards zymosan in primary human macrophages. A knockdown of MFN2 by small interfering RNA decreased mitochondrial respiration without attenuating mitochondrial membrane potential and reduced interactions between endoplasmic reticulum and mitochondria. A MFN2 deficiency potentiated zymosan-elicited inflammatory responses of human primary macrophages, such as expression and secretion of pro-inflammatory cytokines interleukin-1β, -6, -8 and tumor necrosis factor α, as well as induction of cyclooxygenase 2 and prostaglandin E2 synthesis. MFN2 silencing also increased zymosan-induced nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases inflammatory signal transduction, without affecting mitochondrial reactive oxygen species production. Mechanistic studies revealed that MFN2 deficiency enhanced the toll-like receptor 2-dependent branch of zymosan-triggered responses upstream of inhibitor of κB kinase. This was associated with elevated, cytosolic expression of interleukin-1 receptor-associated kinase 4 in MFN2-deficient cells. Our data suggest pro-inflammatory effects of MFN2 deficiency in human macrophages.
KW  - macrophages
KW  - mitochondria
KW  - zymosan
KW  - inflammation
KW  - mitochondrial dynamics
KW  - endoplasmic reticulum
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62423
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-624232
SN  - 1664-3224
N1  - This study was supported by the grants from Deutsche Forschungsgemeinschaft (SFB 1039, Teilprojekt A01, A05, B04, and Z01).
VL  - 12
IS  - art. 723683
SP  - 1
EP  - 15
PB  - Frontiers Media
CY  - Lausanne
ER  -