Year: 2020
Type: dissertation
Abstract: MARITA: Role of MGME1 in rapid degradation of linear mtDNA M.Sc.Thesis (40cp) 65+ 3 appendix Joulukuu, 2019 Mitochondria are cellular organelles, that are critical for cellular viability as they provide ATP through the oxidative phosphorylation pathway (OXPHOS).Mitochondria participate also in other important cellular processes, such as signalling, regulation of ion homeostasis, metabolism of biomolecules and programmed cell death.Mitochondria have their own genome, mitochondrial DNA (mtDNA), which is a 16.6 kb circular DNA molecule.Mitochondria and mtDNA have been studied for decades, and it is understood that the mechanisms of mtDNA replication and maintenance are much more complex and finely regulated processes than previously considered.Damaged mtDNA and loss of mitochondrial genome integrity is being recognized as a contributing factor of neurodegenerative diseases and aging.For understanding mtDNA genomic function and developing effective therapy for mitochondrial related diseases, it is important to understand the mechanism of the maintenance of mtDNA integrity.The aim of this thesis was to survey the role of mitochondrial maintenance exonuclease 1 (MGME1) in the degradation of linear mtDNA.MGME1 has been previously shown to have potential role in mitochondrial maintenance and replication, but its actual biological significance was unclear.The project took advantage of tetracycline-inducible expression of mitochondrially-targeted bacterial restriction enzyme EagI in HEK 293 cells.By using siRNA mediated knockdown, I examined the role of MGME1 as well as other proteins, potentially involved in processing of broken mtDNA, such as PIF1, EXOG, RECQL4 and TWNK in the end-processing of the EagI induced double-strand breaks.The results indicated that the linearized mtDNA molecules are rapidly degraded in MGME1 dependent manner.
Author: Kaislaranta, Marita
Institution: University of Eastern Finland
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7024474284