Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Pavlenko, Victor pavlenkovictor@gmail.com UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-67921
Date:	9 June 2016
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	Life sciences
Uncontrolled Keywords:	Keywords Language mitochondrial biogenesis English Caenorhabditis elegans English gene expression English
Date of oral exam:	27 November 2015
Referee:	Name Academic Title Trifunovic, Aleksandra Prof. Dr. Antebi, Adam Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/6792