2. Academic Validation
  3. SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3

SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3

  • J Biol Chem. 2024 Mar 27:107233. doi: 10.1016/j.jbc.2024.107233.
Feng Xiao 1,  Yaling Jia 2,  Simeng Zhang 3,  Nanfang Liu 2,  Xuelong Zhang 2,  Tianci Wang 4,  Jialu Qiao 5,  Ge Yang 3,  Xu Che 3,  Keli Chen 4,  Pan Pan 2,  Lingli Zhou 6,  Binlian Sun 5,  Jun Chen 7,  Pin Wan 8
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Cognitive and Affective Disorders, Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430072, China; Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China.
  • 2 Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China.
  • 3 Foshan Institute of Medical Microbiology, Foshan 528315, China.
  • 4 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
  • 5 Hubei Key Laboratory of Cognitive and Affective Disorders, Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430072, China.
  • 6 Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China.
  • 7 State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
  • 8 Hubei Key Laboratory of Cognitive and Affective Disorders, Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430072, China; Foshan Institute of Medical Microbiology, Foshan 528315, China. Electronic address: [email protected].
PMID: 38552738 DOI: 10.1016/j.jbc.2024.107233
Abstract

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Keywords

Innate immune response; Mitochondria; NLRP3 inflammasome activation; SLC25A3.

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