Universität zu Köln

Identification of Genes Modulating Mitochondrial Biogenesis in Caenorhabditis elegans

Pavlenko, Victor (2016) Identification of Genes Modulating Mitochondrial Biogenesis in Caenorhabditis elegans. PhD thesis, Universität zu Köln.

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    Abstract

    Since Altmann recognized ubiquitously distributed "bioblasts" in 1890, understanding of mitochondria has evolved from "elementary organisms" living inside cells and carrying out vital functions, over the Harman's "free radical theory" in 1956, to one of the driving forces of aging and cause of multiple associated diseases impacting society today. While a tremendous amount of work has contributed to the understanding of mitochondrial biology in different model organisms, the precise molecular mechanisms of basic mitochondrial function have yet to be deciphered. By employing an RNA interference mediated screen in Caenorhabditis elegans, we identified two transcription factors: SPTF-3, a member of Sp1 family, and an uncharacterized, nematode specific W04D2.4. We propose that both proteins modulate expression of many genes with regard to mitochondrial function including mitochondrial single-stranded binding protein encoded by mtss-1, whose promoter was used as transcriptional reporter in the screen. Further, RNA sequencing data indicate that W04D2.4 indirectly regulates expression of mitochondrial DNA via control of genes functionally related to mitochondrial replication and translation machineries. We also demonstrate that from all interventions targeting cytosolic translation, MTSS-1 levels are elevated only upon knockdown of genes encoding cytosolic ribosomal proteins. Reduction of ribosomes leads to increased sptf-3 translation, most likely in an internal ribosome entry side (IRES) mediated manner, eventually inducing mtss-1 expression. Moreover, we identify a novel role for SPTF-3 in the regulation of mitochondrial unfolded stress response (UPRmt) activation, but not endoplasmatic reticulum or oxidative stress responses. Taken together, this study identifies two transcription factors previously not associated with mitochondrial biogenesis and UPRmt in C. elegans, establishing a basis for further investigation of mito-nuclear interactions.

    Item Type: Thesis (PhD thesis)
    Creators:
    CreatorsEmail
    Pavlenko, Victorpavlenkovictor@gmail.com
    URN: urn:nbn:de:hbz:38-67921
    Subjects: Life sciences
    Uncontrolled Keywords:
    KeywordsLanguage
    mitochondrial biogenesisEnglish
    Caenorhabditis elegansEnglish
    gene expressionEnglish
    Faculty: Mathematisch-Naturwissenschaftliche Fakultät
    Divisions: Mathematisch-Naturwissenschaftliche Fakultät > Institut für Genetik
    Language: English
    Date: 09 June 2016
    Date Type: Publication
    Date of oral exam: 27 November 2015
    Full Text Status: Public
    Date Deposited: 21 Jun 2016 15:44:22
    Referee
    NameAcademic Title
    Trifunovic, AleksandraProf. Dr.
    Antebi, AdamProf. Dr.
    URI: http://kups.ub.uni-koeln.de/id/eprint/6792

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