Lipopolysaccharide promotes Drp1-dependent mitochondrial fission and associated inflammatory responses in macrophages.

Immunology and Cell Biology
Ronan KapetanovicMatthew J Sweet

Abstract

Mitochondria have a multitude of functions, including energy generation and cell signaling. Recent evidence suggests that mitochondrial dynamics (i.e. the balance between mitochondrial fission and fusion) also regulate immune functions. Here, we reveal that lipopolysaccharide (LPS) stimulation increases mitochondrial numbers in mouse bone marrow-derived macrophages (BMMs) and human monocyte-derived macrophages. In BMMs, this response requires Toll-like receptor 4 (Tlr4) and the TLR adaptor protein myeloid differentiation primary response 88 (MyD88) but is independent of mitochondrial biogenesis. Consistent with this phenomenon being a consequence of mitochondrial fission, the dynamin-related protein 1 (Drp1) GTPase that promotes mitochondrial fission is enriched on mitochondria in LPS-activated macrophages and is required for the LPS-mediated increase in mitochondrial numbers in both BMMs and mouse embryonic fibroblasts. Pharmacological agents that skew toward mitochondrial fusion also abrogated this response. LPS triggered acute Drp1 phosphorylation at serine 635 (S635), followed by sustained Drp1 dephosphorylation at serine 656 (S656), in BMMs. LPS-induced S656 dephosphorylation was abrogated in MyD88-deficient BMMs, suggesti...Continue Reading

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Citations

Feb 2, 2021·Frontiers in Cellular and Infection Microbiology·Fushan GaoMary X D O'Riordan
Feb 5, 2021·Free Radical Biology & Medicine·Lei HouXiangrui Wang
May 18, 2021·Frontiers in Immunology·Sally A ClaytonAndrew R Clark
Sep 24, 2021·Immunology and Cell Biology·Anne C La Flamme

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Methods Mentioned

BETA
ELISA
GTPase
PCR
electrophoresis

Software Mentioned

Imaris
GraphPad Prism

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