Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Fulvio Reggiori, Aarhus University, Denmark
- Second opponent: Group leader Alexandra Stolz, Buchman Institute for Molecular Life Sciences, Germany
- Third member and chair of the evaluation committee: Asscoiate Professor Johanne Egge Rinholm, University of Oslo
Chair of the Defence
Associate Professor Coen Campsteijn, University of Oslo
Principal Supervisor
Professor II Anne Gjøen Simonsen, University of Oslo
Summary
Autophagy is a degradative process used by cells to promote survival in stressful conditions and to remove damaged or surplus cellular components, such as toxic aggregates or defective organelles. Autophagic cargo is engulfed by a double membrane, called a phagophore, that expands around the cargo to form an autophagosome that fuses with a lysosome, containing acidic enzymes that degrade the cargo. Autophagosomes are generally devoid of transmembrane proteins, indicating an important role of lipid-binding proteins at different stages of autophagy.
In this thesis, we aimed to identify and characterize novel lipid-binding proteins in selective and non-selective types of autophagy. We identified the PX domain-containing protein sorting nexin 8 (SNX8) as a positive modulator of starvation-induced autophagy and demonstrated that it localizes on early endosomes and lysosomes, regulating autophagosome maturation. We also characterized the endosomal protein SNX10 and found that SNX10 functions as a negative modulator of mitophagy and mitochondrial bioenergetics.
Furthermore, we asked whether different components of the autophagy machinery have distinct functions in different types of autophagy. Intriguingly, we observed that some autophagic components are equally important for selective and non-selective autophagy, while others seem to either inhibit or promote autophagy in a cargo-dependent manner. In conclusion, the data presented in this thesis provide a better understanding of the molecular mechanisms inherent to autophagy, unveiling novel roles for lipid-binding proteins in autophagy.
Additional information
Contact the research support staff.