Involvement of S6K1 in mitochondria function and structure in HeLa cells

Jisoo Park, Quangdon Tran, Kisun Mun, Kouhei Masuda, So Hee Kwon, Seon Hwan Kim, Dong Hoon Kim, George Thomas, Jongsun Park

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)

    Abstract

    The major biological function of mitochondria is to generate cellular energy through oxidative phosphorylation. Apart from cellular respiration, mitochondria also play a key role in signaling processes, including aging and cancer metabolism. It has been shown that S6K1-knockout mice are resistant to obesity due to enhanced beta-oxidation, with an increased number of large mitochondria. Therefore, in this report, the possible involvement of S6K1 in regulating mitochondria dynamics and function has been investigated in stable lenti-shS6K1-HeLa cells. Interestingly, S6K1-stably depleted HeLa cells showed phenotypical changes in mitochondria morphology. This observation was further confirmed by detailed image analysis of mitochondria shape. Corresponding molecular changes were also observed in these cells, such as the induction of mitochondrial fission proteins (Drp1 and Fis1). Oxygen consumption is elevated in S6K1-depeleted HeLa cells and FL5.12 cells. In addition, S6K1 depletion leads to enhancement of ATP production in cytoplasm and mitochondria. However, the relative ratio of mitochondrial ATP to cytoplasmic ATP is actually decreased in lenti-shS6K1-HeLa cells compared to control cells. Lastly, induction of mitophagy was found in lenti-shS6K1-HeLa cells with corresponding changes of mitochondria shape on electron microscope analysis. Taken together, our results indicate that S6K1 is involved in the regulation of mitochondria morphology and function in HeLa cells. This study will provide novel insights into S6K1 function in mitochondria-mediated cellular signaling.

    Original languageEnglish
    Pages (from-to)1904-1915
    Number of pages12
    JournalCellular Signalling
    Volume28
    Issue number12
    DOIs
    Publication statusPublished - 2016 Dec 1

    Bibliographical note

    Funding Information:
    We would like to thank Dr. David Plas (Univ. of Cincinnati) for providing shS6K1-FL5.12 stable cells. This work was financially supported by National Research Foundation of Korea (NRF) grants from the Korean Government (MEST) ( NRF-2012M3A9B6055302 , NRF-2014R1A1A3050752 , NRF-2015R1A2A2A01003597 , NRF-2015R1D1A3A0101569 4 ).

    Publisher Copyright:
    © 2016 Elsevier Inc.

    Copyright:
    Copyright 2017 Elsevier B.V., All rights reserved.

    Keywords

    • Energy metabolism
    • Mitochondria fission
    • S6K1
    • mTOR signaling

    ASJC Scopus subject areas

    • Cell Biology

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