PMID- 37291333
OWN - NLM
STAT- MEDLINE
DCOM- 20230621
LR  - 20231119
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 6
IP  - 1
DP  - 2023 Jun 8
TI  - Carnitine palmitoyltransferase 1A promotes mitochondrial fission by enhancing MFF 
      succinylation in ovarian cancer.
PG  - 618
LID - 10.1038/s42003-023-04993-x [doi]
LID - 618
AB  - Mitochondria are dynamic organelles that are important for cell growth and 
      proliferation. Dysregulated mitochondrial dynamics are highly associated with the 
      initiation and progression of various cancers, including ovarian cancer. However, 
      the regulatory mechanism underlying mitochondrial dynamics is still not fully 
      understood. Previously, our study showed that carnitine palmitoyltransferase 1A 
      (CPT1A) is highly expressed in ovarian cancer cells and promotes the development 
      of ovarian cancer. Here, we find that CPT1A regulates mitochondrial dynamics and 
      promotes mitochondrial fission in ovarian cancer cells. Our study futher shows 
      that CPT1A regulates mitochondrial fission and function through mitochondrial 
      fission factor (MFF) to promote the growth and proliferation of ovarian cancer 
      cells. Mechanistically, we show that CPT1A promotes succinylation of MFF at 
      lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal 
      degradation of MFF. Finally, the study shows that MFF is highly expressed in 
      ovarian cancer cells and that high MFF expression is associated with poor 
      prognosis in patients with ovarian cancer. MFF inhibition significantly inhibits 
      the progression of ovarian cancer in vivo. Overall, CPT1A regulates mitochondrial 
      dynamics through MFF succinylation to promote the development of ovarian cancer. 
      Moreover, our findings suggest that MFF is a potential therapeutic target for 
      ovarian cancer.
CI  - (c) 2023. The Author(s).
FAU - Zhu, Yaqin
AU  - Zhu Y
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Li, Ying
AU  - Li Y
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Li, Zhongqi
AU  - Li Z
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Kong, Wenhui
AU  - Kong W
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Zhao, Xiaoxuan
AU  - Zhao X
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Chen, Shuting
AU  - Chen S
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Yan, Liting
AU  - Yan L
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Wang, Lenan
AU  - Wang L
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Tong, Yunli
AU  - Tong Y
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China.
FAU - Shao, Huanjie
AU  - Shao H
AUID- ORCID: 0000-0002-9377-5117
AD  - National Engineering Laboratory for Resource Developing of Endangered Chinese 
      Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education 
      for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life 
      Sciences, Shaanxi Normal University, 710119, Xi'an, Shaanxi, China. 
      hshao@snnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230608
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - 0 (Mitochondrial Proteins)
RN  - EC 2.3.1.21 (CPT1A protein, human)
SB  - IM
MH  - Female
MH  - Humans
MH  - Carnitine O-Palmitoyltransferase/genetics/metabolism
MH  - Mitochondria/metabolism
MH  - *Mitochondrial Dynamics/physiology
MH  - Mitochondrial Proteins/metabolism
MH  - *Ovarian Neoplasms/genetics/metabolism
PMC - PMC10250469
COIS- The authors declare no competing interests.
EDAT- 2023/06/09 01:09
MHDA- 2023/06/12 06:43
PMCR- 2023/06/08
CRDT- 2023/06/08 23:28
PHST- 2022/10/07 00:00 [received]
PHST- 2023/05/30 00:00 [accepted]
PHST- 2023/06/12 06:43 [medline]
PHST- 2023/06/09 01:09 [pubmed]
PHST- 2023/06/08 23:28 [entrez]
PHST- 2023/06/08 00:00 [pmc-release]
AID - 10.1038/s42003-023-04993-x [pii]
AID - 4993 [pii]
AID - 10.1038/s42003-023-04993-x [doi]
PST - epublish
SO  - Commun Biol. 2023 Jun 8;6(1):618. doi: 10.1038/s42003-023-04993-x.