PMID- 28410208
OWN - NLM
STAT- MEDLINE
DCOM- 20180406
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 26
DP  - 2017 Jun 27
TI  - Tristetraprolin inhibits mitochondrial function through suppression of 
      alpha-Synuclein expression in cancer cells.
PG  - 41903-41920
LID - 10.18632/oncotarget.16706 [doi]
AB  - Mitochondrial dynamics play critical roles in maintaining mitochondrial 
      functions. Here, we report a novel mechanism for regulation of mitochondrial 
      dynamics mediated by tristetraprolin (TTP), an AU-rich element (ARE)-binding 
      protein. Overexpression of TTP resulted in elongated mitochondria, 
      down-regulation of mitochondrial oxidative phosphorylation, reduced membrane 
      potential, cytochrome c release, and increased apoptotic cell death in cancer 
      cells. TTP overexpression inhibited the expression of alpha-Synuclein (alpha-Syn). TTP 
      bound to the ARE within the mRNA 3'-untranslated regions (3'-UTRs) of alpha-Syn and 
      enhanced the decay of alpha-Syn mRNA. Overexpression of alpha-Syn without the 3'-UTR 
      restored TTP-induced defects in mitochondrial morphology, mitochondrial oxidative 
      phosphorylation, membrane potential, and apoptotic cell death. Taken together, 
      our data demonstrate that TTP acts as a regulator of mitochondrial dynamics 
      through enhancing degradation of alpha-Syn mRNA in cancer cells. This finding will 
      increase understanding of the molecular basis of mitochondrial dynamics.
FAU - Vo, Mai-Tram
AU  - Vo MT
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
FAU - Choi, Seong Hee
AU  - Choi SH
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
FAU - Lee, Ji-Heon
AU  - Lee JH
AD  - Department of Stem Cell Biology, School of Medicine, Konkuk University, 
      Gwangjin-Gu, Seoul, 143-701, Korea.
FAU - Hong, Chung Hwan
AU  - Hong CH
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
FAU - Kim, Jong Soo
AU  - Kim JS
AD  - Department of Stem Cell Biology, School of Medicine, Konkuk University, 
      Gwangjin-Gu, Seoul, 143-701, Korea.
FAU - Lee, Unn Hwa
AU  - Lee UH
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
FAU - Chung, Hyung-Min
AU  - Chung HM
AD  - Department of Stem Cell Biology, School of Medicine, Konkuk University, 
      Gwangjin-Gu, Seoul, 143-701, Korea.
FAU - Lee, Byung Ju
AU  - Lee BJ
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
FAU - Park, Jeong Woo
AU  - Park JW
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
FAU - Cho, Wha Ja
AU  - Cho WJ
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (3' Untranslated Regions)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tristetraprolin)
RN  - 0 (alpha-Synuclein)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Adenosine Triphosphate/metabolism
MH  - Apoptosis/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cytochromes c/metabolism
MH  - DNA, Mitochondrial
MH  - GTP Phosphohydrolases/metabolism
MH  - Humans
MH  - Membrane Potential, Mitochondrial
MH  - Mitochondria/*genetics/*metabolism
MH  - Mitochondrial Dynamics
MH  - Neoplasms/*genetics/*metabolism
MH  - Oxygen Consumption
MH  - RNA, Messenger/genetics
MH  - Reactive Oxygen Species/metabolism
MH  - Tristetraprolin/*genetics/*metabolism
MH  - alpha-Synuclein/*genetics
PMC - PMC5522037
OTO - NOTNLM
OT  - mitochondrial dynamics
OT  - tristetraprolin
OT  - alpha-Synuclein
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/04/15 06:00
MHDA- 2018/04/07 06:00
PMCR- 2017/06/27
CRDT- 2017/04/15 06:00
PHST- 2016/12/14 00:00 [received]
PHST- 2017/03/19 00:00 [accepted]
PHST- 2017/04/15 06:00 [pubmed]
PHST- 2018/04/07 06:00 [medline]
PHST- 2017/04/15 06:00 [entrez]
PHST- 2017/06/27 00:00 [pmc-release]
AID - 16706 [pii]
AID - 10.18632/oncotarget.16706 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jun 27;8(26):41903-41920. doi: 10.18632/oncotarget.16706.