PMID- 35478455
OWN - NLM
STAT- MEDLINE
DCOM- 20220715
LR  - 20220801
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 237
IP  - 7
DP  - 2022 Jul
TI  - L-OPA1 deficiency aggravates necroptosis of alveolar epithelial cells through 
      impairing mitochondrial function during acute lung injury in mice.
PG  - 3030-3043
LID - 10.1002/jcp.30766 [doi]
AB  - Necroptosis, a recently described form of programmed cell death, is the main way 
      of alveolar epithelial cells (AECs) death in acute lung injury (ALI). While the 
      mechanism of how to trigger necroptosis in AECs during ALI has been rarely 
      evaluated. Long optic atrophy protein 1 (L-OPA1) is a crucial mitochondrial inner 
      membrane fusion protein, and its deficiency impairs mitochondrial function. This 
      study aimed to investigate the role of L-OPA1 deficiency-mediated mitochondrial 
      dysfunction in AECs necroptosis. We comprehensively investigated the detailed 
      contribution and molecular mechanism of L-OPA1 deficiency in AECs necroptosis by 
      inhibiting or activating L-OPA1. First, our data showed that L-OPA1 expression 
      was downregulated in the lungs and AECs under the lipopolysaccharide (LPS) 
      challenge. Furthermore, inhibition of L-OPA1 aggravated the pathological injury, 
      inflammatory response, and necroptosis in the lungs of LPS-induced ALI mice. In 
      vitro, inhibition of L-OPA1 induced necroptosis of AECs, while activation of 
      L-OPA1 alleviated necroptosis of AECs under the LPS challenge. Mechanistically, 
      inhibition of L-OPA1 aggravated necroptosis of AECs by inducing mitochondrial 
      fragmentation and reducing mitochondrial membrane potential. While activation of 
      L-OPA1 had the opposite effects. In summary, these findings indicate for the 
      first time that L-OPA1 deficiency mediates mitochondrial fragmentation, induces 
      necroptosis of AECs, and exacerbates ALI in mice.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Jiang, Hui-Ling
AU  - Jiang HL
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Hui-Hui
AU  - Yang HH
AUID- ORCID: 0000-0001-7699-3940
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Liu, Yu-Biao
AU  - Liu YB
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Zhang, Chen-Yu
AU  - Zhang CY
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Zhong, Wen-Jing
AU  - Zhong WJ
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Guan, Xin-Xin
AU  - Guan XX
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Jin, Ling
AU  - Jin L
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Hong, Jie-Ru
AU  - Hong JR
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Jin-Tong
AU  - Yang JT
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Tan, Xiao-Hua
AU  - Tan XH
AD  - Experimental Center of Medical Morphology, School of Basic Medicine Science, 
      Central South University, Changsha, Hunan, China.
FAU - Li, Qing
AU  - Li Q
AD  - Department of Physiology, Hunan University of Medicine, Huaihua, Hunan, China.
FAU - Zhou, Yong
AU  - Zhou Y
AUID- ORCID: 0000-0002-7348-2376
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
FAU - Guan, Cha-Xiang
AU  - Guan CX
AUID- ORCID: 0000-0002-8505-8724
AD  - Department of Physiology, School of Basic Medicine Science, Central South 
      University, Changsha, Hunan, China.
LA  - eng
GR  - 91949110/National Natural Science Foundation of China/
GR  - 82170096/National Natural Science Foundation of China/
GR  - 19K103/High School Innovation Fund of Hunan province/
GR  - 202202015410/Health Commission Fund of Hunan province/
GR  - 202202015492/Health Commission Fund of Hunan province/
GR  - 2019zzts893/Fundamental Research Funds for the Central Universities of Central 
      South University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220509
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Lipopolysaccharides)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (Opa1 protein, mouse)
SB  - IM
MH  - *Acute Lung Injury/chemically induced/genetics/metabolism
MH  - *Alveolar Epithelial Cells/metabolism/pathology
MH  - Animals
MH  - GTP Phosphohydrolases/genetics/*metabolism
MH  - Lipopolysaccharides/metabolism/pharmacology
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Necroptosis
OTO - NOTNLM
OT  - L-OPA1
OT  - acute lung injury
OT  - alveolar epithelial cells
OT  - mitochondrial fragmentation
OT  - necroptosis
EDAT- 2022/04/29 06:00
MHDA- 2022/07/16 06:00
CRDT- 2022/04/28 06:05
PHST- 2022/04/18 00:00 [revised]
PHST- 2022/01/20 00:00 [received]
PHST- 2022/04/22 00:00 [accepted]
PHST- 2022/04/29 06:00 [pubmed]
PHST- 2022/07/16 06:00 [medline]
PHST- 2022/04/28 06:05 [entrez]
AID - 10.1002/jcp.30766 [doi]
PST - ppublish
SO  - J Cell Physiol. 2022 Jul;237(7):3030-3043. doi: 10.1002/jcp.30766. Epub 2022 May 
      9.