Leiden University Scholarly Publications

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Deventer, S.J. van (2015)

Tracking the big ones : novel dynamics of organelles and macromolecular complexes during cell division and aging

Doctoral Thesis
In this Thesis we address two important aspects of protein dynamics: protein synthesis and distribution upon cell division and dynamics of the protein degradation machinery. In Chapter 2, we present novel technology (Recombination-Induced Tag Exchange)to distinguish and simultaneously track old and new proteins. In Chapter 3 we usedthis technology to make a comprehensive analysis of the inheritance and synthesis of organelles and macromolecular complexes in budding yeast. Thereby we resolved outstanding issues in organelle synthesis and uncovered symmetrical and asymmetrical patterns of inheritance. Asymmetrical inheritance of organelles and macromolecular complexes may induce lineage differences and could be involved in cell differentiation. Next, we address two aspects of the dynamics of the protein degradation machinery that may be relevant for cellular aging: proteasome localization and degradation of the proteasome. In Chapter 4 we show that the localization of the proteasome,...Show moreIn this Thesis we address two important aspects of protein dynamics: protein synthesis and distribution upon cell division and dynamics of the protein degradation machinery. In Chapter 2, we present novel technology (Recombination-Induced Tag Exchange)to distinguish and simultaneously track old and new proteins. In Chapter 3 we usedthis technology to make a comprehensive analysis of the inheritance and synthesis of organelles and macromolecular complexes in budding yeast. Thereby we resolved outstanding issues in organelle synthesis and uncovered symmetrical and asymmetrical patterns of inheritance. Asymmetrical inheritance of organelles and macromolecular complexes may induce lineage differences and could be involved in cell differentiation. Next, we address two aspects of the dynamics of the protein degradation machinery that may be relevant for cellular aging: proteasome localization and degradation of the proteasome. In Chapter 4 we show that the localization of the proteasome, like its activity, may be a relevant factor in cellular aging and identify genetic factors affecting proteasome localization and longevity in budding yeast. In Chapter 5 we present data that is consistent with lysosomal degradation of damaged proteasomes, which may represent the first sketches of a quality control mechanism for the proteasome.Show less
Proteasome degradation
Proteasome localization
N-terminal acetylation
Cellular aging
Organelle-inheritance
Organelle-synthesis
All authors
Deventer, S.J. van
Supervisor
Neefjes, J.J.
Co-supervisor
Leeuwen, F. van
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine (LUMC), Leiden University
Date
2015-10-21
ISBN (print)
9789462330535

Funding

Sponsorship
Netherlands Proteomics Centre