title: Involvement of S6K1 in mitochondria function and structure in HeLa cells.
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.
authors.affiliation: Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 35015, South Korea; Metabolic Disease Institute, University of Cincinnati, Cincinnati, OH 45437, USA.
authors.forename: Jisoo
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 35015, South Korea.
authors.forename: Quangdon
authors.initials: Q
authors.lastname: Tran
authors.affiliation: Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 35015, South Korea.
authors.forename: Kisun
authors.initials: K
authors.lastname: Mun
authors.affiliation: Metabolic Disease Institute, University of Cincinnati, Cincinnati, OH 45437, USA.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, South Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Neurosurgery, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon 35015, South Korea.
authors.forename: Seon-Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul 02841, South Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Metabolic Disease Institute, University of Cincinnati, Cincinnati, OH 45437, USA.
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 35015, South Korea; Metabolic Disease Institute, University of Cincinnati, Cincinnati, OH 45437, USA. Electronic address: insulin@cnu.ac.kr.
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D063306:Mitophagy / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: Energy metabolism; Mitochondria fission; S6K1; mTOR signaling