PMID- 35745140
OWN - NLM
STAT- MEDLINE
DCOM- 20220627
LR  - 20220716
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 14
IP  - 12
DP  - 2022 Jun 10
TI  - Protective Effect of Mitophagy Regulated by mTOR Signaling Pathway in Liver 
      Fibrosis Associated with Selenium.
LID - 10.3390/nu14122410 [doi]
LID - 2410
AB  - BACKGROUND: As a central organ of energy metabolism, the liver is closely related 
      to selenium for its normal function and disease development. However, the 
      underlying roles of mitochondrial energy metabolism and mitophagy in liver 
      fibrosis associated with selenium remain unclear. METHODS: 28 rats were randomly 
      divided into normal, low-selenium, nano-selenium supplement-1, and supplement-2 
      groups for a 12-week intervention. We observed pathological and ultrastructural 
      changes in the liver and analyzed the effects of selenium deficiency and 
      nano-selenium supplementation on liver metabolic activities and crucial proteins 
      expression of mammalian target of the rapamycin (mTOR) signaling pathway. 
      RESULTS: Selenium deficiency caused liver pathological damage and fibrosis with 
      the occurrence of mitophagy by disrupting normal metabolic activities; meanwhile, 
      the mTOR signaling pathway was up-regulated to enhance mitophagy to clear damaged 
      mitochondria. Furthermore, nano-selenium supplements could reduce the severity of 
      pathological damage and fibrosis in livers and maintain normal energy metabolic 
      activity. With the increased concentrations of nano-selenium supplement, swelling 
      mitochondria and mitophagy gradually decreased, accompanied by the higher 
      expression of mTOR and phosphorylation-modified mTOR proteins and lower 
      expression of unc-51 like autophagy activating kinase 1 (ULK1) and 
      phosphorylation-modified ULK1 proteins. CONCLUSIONS: Mitophagy regulated by the 
      mTOR signaling pathway plays a dual protective role on low-selenium inducing 
      liver fibrosis and nano-selenium supplements preventing liver fibrosis. 
      Mitochondrial energy metabolism plays an important role in these processes as 
      well.
FAU - Qiao, Lichun
AU  - Qiao L
AUID- ORCID: 0000-0002-6739-0846
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Guo, Ziwei
AU  - Guo Z
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Liu, Haobiao
AU  - Liu H
AUID- ORCID: 0000-0003-0843-6899
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Liu, Jiaxin
AU  - Liu J
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Lin, Xue
AU  - Lin X
AUID- ORCID: 0000-0003-4465-7007
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Deng, Huan
AU  - Deng H
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Liu, Xuan
AU  - Liu X
AUID- ORCID: 0000-0002-1526-0361
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Zhao, Yan
AU  - Zhao Y
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Xiao, Xiang
AU  - Xiao X
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
FAU - Lei, Jian
AU  - Lei J
AUID- ORCID: 0000-0001-6707-4280
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Key Lab of Public Health Safety of the Ministry of Education, School of Public 
      Health, Fudan University, Shanghai 200433, China.
FAU - Han, Jing
AU  - Han J
AUID- ORCID: 0000-0003-1460-0114
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
AD  - Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an 
      712000, China.
AD  - Key Laboratory of Environment and Genes Related to Diseases, School of Public 
      Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
LA  - eng
GR  - 81872567/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220610
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - H6241UJ22B (Selenium)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Fibrosis
MH  - Liver Cirrhosis/chemically induced/prevention & control
MH  - Mammals
MH  - *Mitophagy
MH  - Rats
MH  - *Selenium/pharmacology
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
PMC - PMC9227084
OTO - NOTNLM
OT  - energy metabolism
OT  - liver fibrosis
OT  - mTOR signaling pathway
OT  - mitophagy
OT  - selenium
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/28 06:00
PMCR- 2022/06/10
CRDT- 2022/06/24 01:34
PHST- 2022/05/26 00:00 [received]
PHST- 2022/06/04 00:00 [revised]
PHST- 2022/06/07 00:00 [accepted]
PHST- 2022/06/24 01:34 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/28 06:00 [medline]
PHST- 2022/06/10 00:00 [pmc-release]
AID - nu14122410 [pii]
AID - nutrients-14-02410 [pii]
AID - 10.3390/nu14122410 [doi]
PST - epublish
SO  - Nutrients. 2022 Jun 10;14(12):2410. doi: 10.3390/nu14122410.