Investigating mechanisms that ensure partitioning of peroxisomes during cell growth and division

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2023-10-19

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Saudi Digital Library

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Eukaryotic cells contain various organelles, enclosed structures that execute specialized functions, crucial for maintaining cell metabolism under diverse growth conditions. The careful regulation of organelle dynamics and maintenance is central to cell growth and division, and disruptions can lead to a multitude of illnesses in humans. The budding yeast, Saccharomyces cerevisiae, is a model organism that has significantly contributed to our understanding of these processes, leading to the discovery of numerous factors and mechanisms vital for organelle function, many of which are evolutionarily conserved. Eukaryotic cells have developed certain strategies to control the position, quantity and size of their organelles. These mechanisms involve molecular anchors that are vital for the multiplication of organelles, their spatial arrangement, and the creation of inter-organellar contact points. In S. cerevisiae, as in many other cell types, the distribution and dynamics of organelles are indeed critically important. This balance between organelle anchoring and motility does indeed play a key role in determining where organelles are located within the cell and how they are distributed when the cell divides. The distribution of peroxisomes, for example, is controlled through two main mechanisms: anchoring to the cortex in the mother cell and transport towards the bud that is dependent on Myosin. This process is made possible by the Inp1-Pex3 tethering complex which facilitates this transport. Like other organelles, peroxisomes in yeast engage in interactions with various cellular structures. These include the plasma membrane, mitochondria, endoplasmic reticulum, lipid bodies and vacuole. This thesis provides novel insights into the interactions between Inp1, a component of the tethering complex, and the actin cytoskeleton. We found that the initial 100 amino acids of Inp1 (its N-terminal) provide enough capability for binding to actin, revealing a novel connection essential for peroxisome organization. This mechanism is distinct from the Inp2-Myo2-mediated process, indicating the existence of multiple strategies for the organization of peroxisomes and their association with the actin cytoskeleton. Our research also demonstrates that the middle domain of Inp1 interacts with the conserved actin-binding protein Srv2 through its C-terminus. Srv2 demonstrates a strong inclination towards ADP-G-actin and facilitates the recycling of actin monomers, a vital process for the quick turnover of the actin network. Moreover, we discovered an interaction between Srv2 and Vps1, a key protein in peroxisome fission. Based on these findings, we propose a new model for the fission of peroxisomes during asymmetric cell division, where Srv2 functions as a central negative regulator, with its C-terminal playing a critical role in peroxisome regulation.

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yeast, Saccharomyces cerevisiae, organelle inheritance, Inp1, Srv2, actin, CRISPR/Cas9 system

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