PMID- 36338340
OWN - NLM
STAT- MEDLINE
DCOM- 20221108
LR  - 20221108
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Dynamin-Related Protein 1 Is Involved in Mitochondrial Damage, Defective 
      Mitophagy, and NLRP3 Inflammasome Activation Induced by MSU Crystals.
PG  - 5064494
LID - 10.1155/2022/5064494 [doi]
LID - 5064494
AB  - Excessive generation of reactive oxygen species (ROS) has great impacts on MSU 
      crystal-induced inflammation. Drp1-dependent mitochondrial fission is closely 
      associated with mitochondrial ROS levels. However, whether Drp1 signaling 
      contributes to MSU crystal-induced inflammation remains unclear. Mice bone 
      marrow-derived macrophages (BMDMs) were primed with LPS and then stimulated with 
      MSU suspensions for 12 h. The protein levels associated with mitochondrial 
      dynamics, oxidative stress, and mitophagy were detected by Western blot. BMDMs 
      were loaded with MitoTracker Green probe to detect mitochondrial morphology. To 
      measure mitochondrial reactive oxygen species (ROS) and total ROS levels, cells 
      were loaded, respectively, with MitoSOX and DHE probes. The effects of 
      Mito-TEMPO, an antioxidant that targets the mitochondria or DRP1 inhibitor 
      (Mdivi-1) on MSU crystal-induced peritonitis and arthritis mouse models, were 
      evaluated. Our study revealed that MSU crystal stimulation resulted in elevation 
      of mitochondrial fragmentation of BMDMs. Treatment with Mito-TEMPO or Drp1 
      knockdown significantly ameliorated the mitochondrial damage induced by MSU 
      crystals. BMDMs exposure to MSU crystals increased the expression of 
      auto/mitophagy marker proteins and promoted the fusion of mitophagosomes with 
      lysosomes, leading to accumulation of mitolysosomes. Drp1 knockdown alleviated 
      defective mitophagy and activation of the NLRP3 inflammasome in MSU 
      crystal-treated BMDMs. This study indicates that there is crosstalk between 
      mitochondrial ROS and Drp1 signaling in MSU crystal-induced inflammation. Drp1 
      signaling is involved in MSU crystal-induced mitochondrial damage, impaired 
      mitophagy and NLRP3 inflammasome activation.
CI  - Copyright (c) 2022 Hui Jiang et al.
FAU - Jiang, Hui
AU  - Jiang H
AD  - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College 
      and Institute of Rheumatology and Immunology, The Affiliated Hospital of North 
      Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 Sichuan, 
      China.
AD  - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of 
      North Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 
      Sichuan, China.
FAU - Chen, Feng
AU  - Chen F
AD  - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College 
      and Institute of Rheumatology and Immunology, The Affiliated Hospital of North 
      Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 Sichuan, 
      China.
AD  - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of 
      North Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 
      Sichuan, China.
FAU - Song, DianZe
AU  - Song D
AD  - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College 
      and Institute of Rheumatology and Immunology, The Affiliated Hospital of North 
      Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 Sichuan, 
      China.
AD  - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of 
      North Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 
      Sichuan, China.
FAU - Zhou, Xiaoqin
AU  - Zhou X
AD  - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College 
      and Institute of Rheumatology and Immunology, The Affiliated Hospital of North 
      Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 Sichuan, 
      China.
FAU - Ren, Long
AU  - Ren L
AUID- ORCID: 0000-0002-5542-3735
AD  - The Fifth People's Hospital of Nanchong City, 21# Bajiao Street, Nanchong, 637100 
      Sichuan, China.
FAU - Zeng, Mei
AU  - Zeng M
AUID- ORCID: 0000-0002-5661-7101
AD  - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College 
      and Institute of Rheumatology and Immunology, The Affiliated Hospital of North 
      Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 Sichuan, 
      China.
AD  - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of 
      North Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, 637001 
      Sichuan, China.
AD  - The Fifth People's Hospital of Nanchong City, 21# Bajiao Street, Nanchong, 637100 
      Sichuan, China.
LA  - eng
PT  - Journal Article
DEP - 20221025
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 3.6.5.5 (Dynamins)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Mitophagy
MH  - *Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Dynamins/metabolism
MH  - Mitochondrial Dynamics
MH  - Inflammation
PMC - PMC9627272
COIS- The authors declare that they have no competing interests.
EDAT- 2022/11/08 06:00
MHDA- 2022/11/09 06:00
PMCR- 2022/10/25
CRDT- 2022/11/07 04:26
PHST- 2022/07/18 00:00 [received]
PHST- 2022/09/21 00:00 [accepted]
PHST- 2022/11/07 04:26 [entrez]
PHST- 2022/11/08 06:00 [pubmed]
PHST- 2022/11/09 06:00 [medline]
PHST- 2022/10/25 00:00 [pmc-release]
AID - 10.1155/2022/5064494 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Oct 25;2022:5064494. doi: 10.1155/2022/5064494. 
      eCollection 2022.