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Peroxisomal membrane protein degradation in yeast

Devarajan, S., 2020, [Groningen]: University of Groningen. 199 p.

Research output: ThesisThesis fully internal (DIV)

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  • Srishti Devarajan
Peroxisomes are single membrane-bound organelles that are present in nearly all eukaryotic cells. Some well-known peroxisome functions include β-oxidation of fatty acids, synthesis of plasmalogens and detoxification of hydrogen peroxide, but many more exist. Peroxisomal functions are largely determined by peroxisomal matrix proteins and peroxisomal membrane proteins (PMPs). Thus, peroxisomal proteins need to be tightly controlled through regulation of protein synthesis, targeting as well as protein degradation. Peroxisomal proteins may undergo degradation either because they are damaged/unfolded by various stress factors or because they are no longer needed. Protein degradation needs to be tightly controlled in order to prevent the accumulation of unwanted proteins or the occurrence of unwanted protein degradation events. While many efforts have been placed on studying the post-translational targeting of PMPs to peroxisomes, little is known about PMP degradation. Investigating which PMPs are targeted for degradation, how and why PMPs are degraded will allow us to better understand the role of PMP degradation in a cellular context. The research presented in this thesis provides insights into PMP degradation in the yeast Saccharomyces cerevisiae. Using the tandem fluorescent timer (tFT) approach which employs two fluorescent proteins of different maturation kinetics, we investigated the stability of PMP-tFT fusions and identified two unstable proteins (Pxa1-tFT and Pex13-tFT) that are rapidly degraded from peroxisomes. Furthermore using the same approach, we also identified for the first time that in addition to peroxisomal Ubiquitin Proteasome System (UPS) components, cytosolic proteins also function in the degradation of unstable PMP-tFT fusions as well as a mutant form of Pxa1p. Lastly, we show that like other organelles such as ER, peroxisomes possess a quality control system to remove faulty proteins.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date18-Sep-2020
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-2619-8
Electronic ISBNs978-94-034-2618-1
Publication statusPublished - 2020

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