PMID- 36692416
OWN - NLM
STAT- MEDLINE
DCOM- 20230130
LR  - 20230222
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 37
IP  - 2
DP  - 2023 Feb
TI  - Neuroprotective effects of melatonin-mediated mitophagy through 
      nucleotide-binding oligomerization domain and leucine-rich repeat-containing 
      protein X1 in neonatal hypoxic-ischemic brain damage.
PG  - e22784
LID - 10.1096/fj.202201523R [doi]
AB  - Hypoxia-ischemia (HI) is a major cause of brain damage in neonates. Mitochondrial 
      dysfunction acts as a hub for a broad spectrum of signaling events, culminating 
      in cell death triggered by HI. A neuroprotective role of melatonin (MT) has been 
      proposed, and mitophagy regulation seems to be important for cell survival. 
      However, the molecular mechanisms underlying MT-mediated mitophagy during HI 
      treatment are poorly defined. Nucleotide-binding oligomerization domain and 
      leucine-rich repeat-containing protein X1 (NLRX1) has emerged as a critical 
      regulator of mitochondrial dynamics and neuronal death that participates in the 
      pathology of diverse diseases. This study aimed to clarify whether NLRX1 
      participates in the regulation of mitophagy during MT treatment for 
      hypoxic-ischemic brain damage (HIBD). We demonstrated that MT protected neonates 
      from HIBD through NLRX1-mediated mitophagy in vitro and in vivo. Meanwhile, MT 
      upregulated the expression of NLRX1, Beclin-1, and autophagy-related 7 (ATG7) but 
      decreased the expression of the mammalian target of rapamycin (mTOR) and 
      translocase of the inner membrane of mitochondrion 23 (TIM23). Moreover, the 
      neuroprotective effects of MT were abolished by silencing NLRX1 after 
      oxygen-glucose deprivation (OGD). In addition, the downregulation of mTOR and 
      upregulation of Beclin-1 and ATG7 by MT were inhibited after silencing NLRX1 
      under OGD. In summary, MT modulates mitophagy induction through NLRX1 and plays a 
      protective role in HIBD, providing insight into potential therapeutic targets for 
      MT to exert neuroprotection.
CI  - (c) 2023 Federation of American Societies for Experimental Biology.
FAU - Zhang, Yi
AU  - Zhang Y
AUID- ORCID: 0000-0003-0975-1495
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang City, P.R. China.
FAU - Chen, Dan
AU  - Chen D
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang City, P.R. China.
FAU - Wang, Yiwei
AU  - Wang Y
AD  - Department of Human Anatomy, College of Basic Medical Sciences, Shenyang Medical 
      College, Shenyang City, P.R. China.
AD  - Department of Pathology, College of Basic Medical Sciences, Shenyang Medical 
      College, Shenyang City, P.R. China.
FAU - Wang, Xingzao
AU  - Wang X
AD  - Department of Clinical Medicine, College of Basic Medical Sciences, Shenyang 
      Medical College, Shenyang City, P.R. China.
FAU - Zhang, Zhong
AU  - Zhang Z
AD  - Department of Pathology, College of Basic Medical Sciences, Shenyang Medical 
      College, Shenyang City, P.R. China.
FAU - Xin, Ying
AU  - Xin Y
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang City, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Beclin-1)
RN  - IY9XDZ35W2 (Glucose)
RN  - GMW67QNF9C (Leucine)
RN  - JL5DK93RCL (Melatonin)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (NLRX1 protein, human)
RN  - 0 (Nucleotides)
RN  - S88TT14065 (Oxygen)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Infant, Newborn
MH  - Beclin-1/metabolism
MH  - Brain/metabolism
MH  - Glucose/pharmacology
MH  - Hypoxia/drug therapy
MH  - *Hypoxia-Ischemia, Brain/metabolism
MH  - Leucine/pharmacology
MH  - *Melatonin/pharmacology
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - Mitophagy
MH  - *Neuroprotective Agents/pharmacology/therapeutic use
MH  - Nucleotides
MH  - Oxygen/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - NLRX1
OT  - apoptosis
OT  - brain damage
OT  - hypoxia-ischemia
OT  - melatonin
OT  - mitophagy
OT  - neonates
OT  - neuroprotective
EDAT- 2023/01/25 06:00
MHDA- 2023/01/27 06:00
CRDT- 2023/01/24 10:12
PHST- 2022/12/14 00:00 [revised]
PHST- 2022/09/23 00:00 [received]
PHST- 2023/01/09 00:00 [accepted]
PHST- 2023/01/24 10:12 [entrez]
PHST- 2023/01/25 06:00 [pubmed]
PHST- 2023/01/27 06:00 [medline]
AID - 10.1096/fj.202201523R [doi]
PST - ppublish
SO  - FASEB J. 2023 Feb;37(2):e22784. doi: 10.1096/fj.202201523R.