Disputas – Master of Science Yakubu Princely Abudu
Master of Science Yakubu Princely Abudu disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen:
“Roles of SAMM50 and NIPSNAP Family Proteins in Mitophagy”
Kort sammendrag av avhandlingen:
Autophagy (greek: “self-eating”) is a renovation process whereby our cells get rid of damaged or harmful components by degrading them in the lysosome. The lysosomes are the cell’s destruction factories and recycling units. To get to the lysosome the cells tag the material destined for degradation, and the tagged material is encapsulated into a double-membrane vesicle called the autophagosome. This is a vehicle carrying the waste to the lysosome where it is degraded and building blocks are recycled. Our cells contain membrane enclosed units called organelles that carry out specific functions. One such type of organelle is the mitochondria. They act as power stations within the cell and produce energy needed for the daily life of the cell. When mitochondria gets damaged, the damaged parts need to be replaced. If the damage is too extensive whole mitochondria need to be degraded to avoid harm to the cells as damaged mitochondria pollute and produce toxic waste. The damaged mitochondria are degraded by a selective autophagy process called mitophagy.
Basal mitophagy occurs under normal conditions to maintain mitochondrial function by replacing parts. However, various stress or damages to the mitochondria can also induce degradation of whole mitochondria. Stress- or damage-induced mitophagy is mediated by the kinase PINK1 and the E3 ubiquitin-protein ligase Parkin. Mutations in PINK1 and Parkin are associated with the neurodegenerative disorder Parkinson’s disease. However, the signals that determine how and which mitochondria are degraded are not properly identified yet.
The PhD thesis work of Yakubu Princely Abudu carried out in Molecular Cancer Research Group, guided by Professor Terje Johansen, addresses both basal- and stress-induced mitophagy. In this study, it is demonstrated that the mitochondrial proteins, NIPSNAP1 and NIPSNAP2, actually act as “eat-me” signals for removal of damaged mitochondria by mitophagy. The NIPSNAP proteins tag the outside of damaged mitochondria to signal to the renovator crew (the selective atuophagy receptors). While we have some knowledge about the mechanisms of stress- or damage-induced mitophagy, little is known about the mechanisms of basal mitophagy. In this study, it is shown that the mitochondrial protein SAMM50 mediates basal mitophagy through recruitment of ATG8 family proteins and the autophagy receptor p62. This enables the replacements of parts of the mitochondria required for their energy production without degrading whole mitochondria. Our findings represent important contributions to the understanding of how cells carry out quality control of their mitochondria and destroy damaged mitochondria that can harm the cells. This knowledge has implications for aging, neurodegenerative diseases and cancer.
Hovedveileder professor Terje Johansen
Biveileder førsteamanuensis Trond Lamark
Programme Leader Ian Ganley, University of Dundee, UK – 1. opponent Reader in Cell Biology
Jon Lane, University of Bristol, UK – 2. opponent
Professor Ingvild Mikkola, UiT – Norges arktiske universitet – leder av komité
Professor Ørjan Olsvik, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet
Prøveforelesning over oppgitt emne holdes kl. 10.15, samme sted: “The causes and consequences of Mitochondrial Disease”