PMID- 35438433
OWN - NLM
STAT- MEDLINE
DCOM- 20220531
LR  - 20220531
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 59
IP  - 6
DP  - 2022 Jun
TI  - Acetaldehyde Induces Cytotoxicity via Triggering Mitochondrial Dysfunction and 
      Overactive Mitophagy.
PG  - 3933-3946
LID - 10.1007/s12035-022-02828-0 [doi]
AB  - Overconsumption of alcohol damages brain tissue and causes cognitive dysfunction. 
      It has been suggested that the neurotoxicity caused by excessive alcohol 
      consumption is largely mediated by acetaldehyde, the most toxic metabolite of 
      ethanol. Evidence shows that acetaldehyde impairs mitochondrial function and 
      induces cytotoxicity of neuronal cells; however, the exact mechanisms are not 
      fully understood. The aim of this study was to investigate the role of mitophagy 
      in acetaldehyde-induced cytotoxicity. It was found that acetaldehyde treatment 
      induced mitophagic responses and caused cytotoxicity in SH-SY5Y cells. The levels 
      of light chain 3 (LC3)-II, Beclin1, autophagy-related protein (Atg) 5 and 
      Atg16L1, PTEN-induced putative kinase (PINK)1, and Parkin were significantly 
      elevated, while the level of p62 was reduced in acetaldehyde-treated cells. 
      Acetaldehyde also promoted the accumulation of PINK1 and Parkin on mitochondria 
      and caused a remarkable decrease of mitochondrial mass. Treatment with autophagy 
      inhibitors prevented the decline of mitochondrial mass and alleviated the 
      cytotoxicity induced by acetaldehyde, suggesting that overactive mitophagy might 
      be an important mechanism contributing to acetaldehyde-induced cytotoxicity. 
      Antioxidant N-acetyl-L-cysteine significantly attenuated the mitophagic responses 
      and alleviated the cytotoxicity induced by acetaldehyde, indicating that 
      oxidative stress was a major mediator of the excessive mitophagy induced by 
      acetaldehyde. Taken together, these findings provided new insights into the role 
      of mitophagy and oxidative stress in acetaldehyde-induced cytotoxicity.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Yan, Tingting
AU  - Yan T
AD  - Department of Bioengineering, Harbin Institute of Technology, Weihai, 264209, 
      Shandong, China.
FAU - Zhao, Yan
AU  - Zhao Y
AUID- ORCID: 0000-0002-9211-0092
AD  - Department of Bioengineering, Harbin Institute of Technology, Weihai, 264209, 
      Shandong, China. zhaoyan@hitwh.edu.cn.
FAU - Jiang, Zhongyu
AU  - Jiang Z
AD  - Department of Bioengineering, Harbin Institute of Technology, Weihai, 264209, 
      Shandong, China.
FAU - Chen, Jiyang
AU  - Chen J
AD  - Department of Bioengineering, Harbin Institute of Technology, Weihai, 264209, 
      Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20220419
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
RN  - GO1N1ZPR3B (Acetaldehyde)
SB  - IM
MH  - *Acetaldehyde/metabolism/toxicity
MH  - Mitochondria/metabolism
MH  - *Mitophagy/physiology
MH  - Protein Kinases/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Ubiquitin-Protein Ligases/metabolism
OTO - NOTNLM
OT  - Acetaldehyde
OT  - Drp1
OT  - Mitophagy
OT  - PINK1
OT  - Parkin
OT  - Reactive oxygen species
EDAT- 2022/04/20 06:00
MHDA- 2022/06/01 06:00
CRDT- 2022/04/19 12:08
PHST- 2021/11/21 00:00 [received]
PHST- 2022/04/02 00:00 [accepted]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/06/01 06:00 [medline]
PHST- 2022/04/19 12:08 [entrez]
AID - 10.1007/s12035-022-02828-0 [pii]
AID - 10.1007/s12035-022-02828-0 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2022 Jun;59(6):3933-3946. doi: 10.1007/s12035-022-02828-0. Epub 
      2022 Apr 19.