PhD defence: Structural insights into protein biogenesis on the mitochondrial surface

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Mitochondria are the powerplants of our cells and need many different proteins to perform their vital functions. However, not only the proteins themselves are important for mitochondrial function, but also their correct abundance, distribution, and interactions with other mitochondrial proteins.

Despite the presence of a mitochondrial genome and translation machinery, most mitochondrial proteins are synthesized by cytosolic ribosomes and need to be imported into the mitochondria. Ribosomes not only synthesize proteins distributed in the cytosol, but also synthesize proteins locally, for example on the surface of organelles.

In this thesis I aimed to improve our understanding of the cytosolic ribosome-mitochondria association, polyribosome organization and states of translation on the mitochondrial surface. For this, we established fast and gentle purification protocols optimized for cryo-ET for yeast (S. cerevisiae) and human (HEK293) mitochondria, used the translation inhibitor CHX to stabilize RNCs attached to mitochondria and subsequently analysed ribosome 3D organization, states of translation and OMM attachment, using cryo-ET and subtomogram averaging.

The observations made in this thesis illustrate how extensions to a core machinery, in this case rRNA expansion segments on cytosolic ribosomes, can modulate and mediated interactions with different sub-cellular environments. In addition, our research also opened up several follow-up questions for future research on translation, as well as on ribosome hibernation on the mitochondrial surface.

Start date and time
End date and time
Location
Academiegebouw, Domplein 29 & online (livestream link)
PhD candidate
L.M.K. Thärichen
Dissertation
Structural insights into protein biogenesis on the mitochondrial surface
PhD supervisor(s)
prof. dr. F.G. Förster
Co-supervisor(s)
dr. S.C. Howes
More information
Abstract via Utrecht University Repository