Macrophage NRF1 promotes mitochondrial protein turnover via the ubiquitin proteasome system to limit mitochondrial stress and inflammation.
Macrophage elaboration of inflammatory responses is dynamically regulated, shifting from acute induction to delayed suppression during the course of infection. Here, we show that such regulation of inflammation is modulated by dynamic shifts in metabolism. In macrophages exposed to the bacterial product lipopolysaccharide (LPS), an initial induction of protein biosynthesis is followed by compensatory induction of the transcription factor nuclear factor erythroid 2-like 1 (NRF1), leading to increased flux through the ubiquitin proteasome system (UPS). A major target of NRF1-mediated UPS flux is the mitochondrial proteome, and in the absence of NRF1, ubiquitinated mitochondrial proteins accumulate to trigger severe mitochondrial stress. Such mitochondrial stress engages the integrated stress response-ATF4 axis, which limits mitochondrial translation to attenuate mitochondrial stress but amplifies inflammatory responses to augment susceptibility to septic shock. Therefore, NRF1 mediates a dynamic regulation of mitochondrial proteostasis in inflammatory macrophages that contributes to curbing inflammatory responses.
Pubmed ID: 39325625 RIS Download
Additional research tools detected in this publication
None foundAntibodies used in this publication
- VDAC1 Rabbit mAb (RRID:AB_2862746)
- Goat Anti-Mouse IgG H&L (Alexa Fluor 488) preadsorbed Antibody (RRID:AB_2688012)
- Goat anti-Rabbit IgG (Heavy Chain), Superclonal Recombinant Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2536097)
- Mouse Anti-Mouse CD64 a and b Alloantigens Antibody, Alexa Fluor??? 647 Conjugated (RRID:AB_647120)
- PE anti-mouse CD19 (RRID:AB_2629817)
- Brilliant Violet 785(TM) anti-mouse CD8a (RRID:AB_2562610)
- Brilliant Violet 605(TM) anti-mouse CD4 (RRID:AB_2563054)
- Rabbit Anti-eIF2alpha, phospho (Ser51) Monoclonal Antibody, Unconjugated, Clone 119A11 (RRID:AB_390740)
- PE/Cyanine7 anti-mouse/human CD11b (RRID:AB_312799)
- APC anti-mouse F4/80 (RRID:AB_893481)
- Mouse Anti-Proteasome 19S Rpt5 / S6a subunit Monoclonal Antibody, Unconjugated, Clone TBP1-19 (RRID:AB_2052361)
- Rabbit Anti-HRI Polyclonal antibody, Unconjugated, Clone Not applicable (RRID:AB_441964)
- PERK (C33E10) Rabbit mAb (RRID:AB_2095847)
- [KO Validated] LC3B Rabbit mAb (RRID:AB_2862723)
- Phospho-eIF2α-S51 Rabbit mAb (RRID:AB_2863809)
- Beta Actin antibody (RRID:AB_10700003)
- TCF11/NRF1 (D5B10) Rabbit mAb (RRID:AB_11178947)
- Lamin A/C (E-1) (RRID:AB_10991536)
- Purified anti-Ubiquitin (RRID:AB_1659269)
- GAPDH Rabbit mAb (RRID:AB_2862549)
- Anti-Puromycin Antibody, clone 12D10 (RRID:AB_2566826)
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This is a list of tools and resources that we have found mentioned in this publication.
Goat Anti-Mouse IgG H&L (Alexa Fluor 488) preadsorbed Antibody (antibody)
RRID:AB_2688012
This polyclonal targets Mouse IgG H&L
View all literature mentionsGoat anti-Rabbit IgG (Heavy Chain), Superclonal Recombinant Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2536097
This recombinant polyclonal secondary targets IgG (Heavy Chain)
View all literature mentionsMouse Anti-Mouse CD64 a and b Alloantigens Antibody, Alexa Fluor??? 647 Conjugated (antibody)
RRID:AB_647120
This unknown targets CD64 a and b Alloantigens
View all literature mentionsPE anti-mouse CD19 (antibody)
RRID:AB_2629817
This monoclonal targets CD19
View all literature mentionsBrilliant Violet 785(TM) anti-mouse CD8a (antibody)
RRID:AB_2562610
This monoclonal targets CD8a
View all literature mentionsBrilliant Violet 605(TM) anti-mouse CD4 (antibody)
RRID:AB_2563054
This monoclonal targets CD4
View all literature mentionsRabbit Anti-eIF2alpha, phospho (Ser51) Monoclonal Antibody, Unconjugated, Clone 119A11 (antibody)
RRID:AB_390740
This monoclonal targets Phospho-eIF2 alpha (Ser51)
View all literature mentionsPE/Cyanine7 anti-mouse/human CD11b (antibody)
RRID:AB_312799
This monoclonal targets CD11b
View all literature mentionsAPC anti-mouse F4/80 (antibody)
RRID:AB_893481
This monoclonal targets F4/80
View all literature mentionsMouse Anti-Proteasome 19S Rpt5 / S6a subunit Monoclonal Antibody, Unconjugated, Clone TBP1-19 (antibody)
RRID:AB_2052361
This monoclonal targets Proteasome 19S Rpt5 / S6a subunit
View all literature mentionsRabbit Anti-HRI Polyclonal antibody, Unconjugated, Clone Not applicable (antibody)
RRID:AB_441964
This polyclonal targets HRI
View all literature mentionsPERK (C33E10) Rabbit mAb (antibody)
RRID:AB_2095847
This monoclonal targets PERK (C33E10) Rabbit mAb
View all literature mentions[KO Validated] LC3B Rabbit mAb (antibody)
RRID:AB_2862723
This monoclonal targets
View all literature mentionsPhospho-eIF2α-S51 Rabbit mAb (antibody)
RRID:AB_2863809
This unknown targets
View all literature mentionsBeta Actin antibody (antibody)
RRID:AB_10700003
This polyclonal targets Beta Actin
View all literature mentionsTCF11/NRF1 (D5B10) Rabbit mAb (antibody)
RRID:AB_11178947
This monoclonal targets TCF11/NRF1 (D5B10) Rabbit mAb
View all literature mentionsLamin A/C (E-1) (antibody)
RRID:AB_10991536
This monoclonal targets Lamin A/C (E-1)
View all literature mentionsPurified anti-Ubiquitin (antibody)
RRID:AB_1659269
This monoclonal targets Ubiquitin
View all literature mentionsAnti-Puromycin Antibody, clone 12D10 (antibody)
RRID:AB_2566826
This monoclonal targets Puromycin from Streptomyces alboniger
View all literature mentionsB6(C)-Gt(ROSA)26Sorem1.1(CAG-cas9*.-EGFP)Rsky/J (organism)
RRID:IMSR_JAX:028555
Mus musculus with name B6(C)-Gt(ROSA)26Sorem1.1(CAG-cas9*.-EGFP)Rsky/J from IMSR.
View all literature mentionsC57BL/6JGpt-Lyz2em1Cin(iCre)/Gpt (organism)
RRID:IMSR_GPT:T003822
Mus musculus with name C57BL/6JGpt-Lyz2em1Cin(iCre)/Gpt from IMSR.
View all literature mentionsC57BL/6JGpt-Nfe2l1em1Cflox/Gpt (organism)
RRID:IMSR_GPT:T016349
Mus musculus with name C57BL/6JGpt-Nfe2l1em1Cflox/Gpt from IMSR.
View all literature mentions
