Oncotarget

Research Papers:

Tristetraprolin inhibits mitochondrial function through suppression of α-Synuclein expression in cancer cells

Mai-Tram Vo, Seong Hee Choi, Ji-Heon Lee, Chung Hwan Hong, Jong Soo Kim, Unn Hwa Lee, Hyung-Min Chung, Byung Ju Lee, Jeong Woo Park and Wha Ja Cho _

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Oncotarget. 2017; 8:41903-41920. https://doi.org/10.18632/oncotarget.16706

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Abstract

Mai-Tram Vo1, Seong Hee Choi1, Ji-Heon Lee2, Chung Hwan Hong1, Jong Soo Kim2, Unn Hwa Lee1, Hyung-Min Chung2, Byung Ju Lee1, Jeong Woo Park1 and Wha Ja Cho1

1Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea

2Department of Stem Cell Biology, School of Medicine, Konkuk University, Gwangjin-Gu, Seoul, 143-701, Korea

Correspondence to:

Jeong Woo Park, email: jwpark@ulsan.ac.kr

Wha Ja Cho, email: wjcho26@ulsan.ac.kr

Keywords: tristetraprolin, mitochondrial dynamics, α-Synuclein

Received: December 14, 2016     Accepted: March 19, 2017     Published: March 30, 2017

ABSTRACT

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 α-Synuclein (α-Syn). TTP bound to the ARE within the mRNA 3'-untranslated regions (3′-UTRs) of α-Syn and enhanced the decay of α-Syn mRNA. Overexpression of α-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 α-Syn mRNA in cancer cells. This finding will increase understanding of the molecular basis of mitochondrial dynamics.


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