PMID- 34943057
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230729
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 12
DP  - 2021 Dec 6
TI  - Mito-TIPTP Increases Mitochondrial Function by Repressing the Rubicon-p22phox 
      Interaction in Colitis-Induced Mice.
LID - 10.3390/antiox10121954 [doi]
LID - 1954
AB  - The run/cysteine-rich-domain-containing Beclin1-interacting autophagy protein 
      (Rubicon) is essential for the regulation of nicotinamide adenine dinucleotide 
      phosphate (NADPH) oxidase by interacting with p22phox to trigger the production 
      of reactive oxygen species (ROS) in immune cells. In a previous study, we 
      demonstrated that the interaction of Rubicon with p22phox increases cellular ROS 
      levels. The correlation between Rubicon and mitochondrial ROS (mtROS) is poorly 
      understood. Here, we report that Rubicon interacts with p22phox in the outer 
      mitochondrial membrane in macrophages and patients with human ulcerative colitis. 
      Upon lipopolysaccharide (LPS) activation, the binding of Rubicon to p22phox was 
      elevated, and increased not only cellular ROS levels but also mtROS, with an 
      impairment of mitochondrial complex III and mitochondrial biogenesis in 
      macrophages. Furthermore, increased Rubicon decreases mitochondrial metabolic 
      flux in macrophages. Mito-TIPTP, which is a p22phox inhibitor containing a 
      mitochondrial translocation signal, enhances mitochondrial function by inhibiting 
      the association between Rubicon and p22phox in LPS-primed bone-marrow-derived 
      macrophages (BMDMs) treated with adenosine triphosphate (ATP) or dextran sulfate 
      sodium (DSS). Remarkably, Mito-TIPTP exhibited a therapeutic effect by decreasing 
      mtROS in DSS-induced acute or chronic colitis mouse models. Thus, our findings 
      suggest that Mito-TIPTP is a potential therapeutic agent for colitis by 
      inhibiting the interaction between Rubicon and p22phox to recover mitochondrial 
      function.
FAU - Kim, Jae-Sung
AU  - Kim JS
AD  - Department of Bionano Technology, Hanyang University, Seoul 04673, Korea.
AD  - Institute of Natural Science & Technology, Hanyang University, Ansan 15588, 
      Korea.
FAU - Kim, Ye-Ram
AU  - Kim YR
AD  - Department of Bionano Technology, Hanyang University, Seoul 04673, Korea.
FAU - Jang, Sein
AU  - Jang S
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
AD  - Department of Molecular and Life Science, Hanyang University, Ansan 15588, Korea.
FAU - Wang, Sang Geon
AU  - Wang SG
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
AD  - Department of Applied Chemistry, Hanyang University, Ansan 15588, Korea.
FAU - Cho, Euni
AU  - Cho E
AD  - Department of Bionano Technology, Hanyang University, Seoul 04673, Korea.
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
FAU - Mun, Seok-Jun
AU  - Mun SJ
AD  - Department of Bionano Technology, Hanyang University, Seoul 04673, Korea.
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
FAU - Jeon, Hye-In
AU  - Jeon HI
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
AD  - Department of Molecular and Life Science, Hanyang University, Ansan 15588, Korea.
FAU - Kim, Hyo-Keun
AU  - Kim HK
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
AD  - Department of Molecular and Life Science, Hanyang University, Ansan 15588, Korea.
FAU - Min, Sun-Joon
AU  - Min SJ
AUID- ORCID: 0000-0003-0867-4416
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
AD  - Department of Applied Chemistry, Hanyang University, Ansan 15588, Korea.
AD  - Department of Chemical & Molecular Engineering, Hanyang University, Ansan 15588, 
      Korea.
FAU - Yang, Chul-Su
AU  - Yang CS
AUID- ORCID: 0000-0003-4918-961X
AD  - Center for Bionano Intelligence Education and Research, Ansan 15588, Korea.
AD  - Department of Molecular and Life Science, Hanyang University, Ansan 15588, Korea.
LA  - eng
GR  - 2021R1A4A5032463/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20211206
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
EIN - Antioxidants (Basel). 2023 Jul 13;12(7):. PMID: 37508020
PMC - PMC8750874
OTO - NOTNLM
OT  - Rubicon
OT  - colitis
OT  - mitochondria
OT  - p22phox
OT  - reactive oxygen species
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2021/12/25 06:01
PMCR- 2021/12/06
CRDT- 2021/12/24 01:01
PHST- 2021/10/28 00:00 [received]
PHST- 2021/11/29 00:00 [revised]
PHST- 2021/12/03 00:00 [accepted]
PHST- 2021/12/24 01:01 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2021/12/25 06:01 [medline]
PHST- 2021/12/06 00:00 [pmc-release]
AID - antiox10121954 [pii]
AID - antioxidants-10-01954 [pii]
AID - 10.3390/antiox10121954 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Dec 6;10(12):1954. doi: 10.3390/antiox10121954.