Targeting carbonic anhydrase IX by nitroimidazole based sulfamides enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting drugs

n/

Peroxisome formation and dynamics in yeast

Peroxisomes are characteristic organelles of eukaryotic cells. These organelles may perform various functions dependent on cell type and environmental needs For long, there has been a strong debate in the field of how peroxisomes are formed.The aim of the research was to obtain further insights into the process of peroxisome formation (fission, inheritance and peroxisome formation from the ER) with emphasis on proteins involved in these processes, using the yeast Hansenula polymorpha as principal model organism. We demonstrate that in H. polymorpha peroxisome fission is the major pathway of peroxisome proliferation. Deletion of DNM1 resulted in a single peroxisome which formed long protrusions in the newly formed bud that did not divide until during cytokinesis. We also show that Dnm1 and Vps1 are not required for peroxisome formation from the ER.We next studied the role of Pex11 family members in peroxisome reintroduction from the ER. Pex25, but not Pex11 and Pex11c, were observed to play a role in this process as peroxisomes could not be reintroduced in pex3 pex25 strain. Additionally our studies indicate that Ypt7 (a protein involved in vacuolar fusion) is involved in peroxisome fission. We also analyzed peroxisome inheritance in H. polymorpha. In this study we have identified Inp1- and Inp2- related proteins in 18 budding yeast species, indicating that both proteins are highly conserved in yeast. Additionally, we demonstrated that the identified putative H. polymorpha Inp2 is localized to peroxisomes and the deletion of INP2 resulted in a defect in peroxisome inheritance to bud cells.

Peroxisomes as dynamic organelles: peroxisome abundance in yeast

Peroxisomes are cell organelles that are present in almost all eukaryotic cells and involved in a large range of metabolic pathways. The organelles are highly dynamic in nature: their number and enzyme content is highly variable and continuously adapts to prevailing environmental conditions. This review summarizes recent relevant developments in research on processes that are involved in the regulation of peroxisome abundance and maintenance. These processes include fission of the organelles, formation of new peroxisomes from the endoplasmic reticulum, autophagic degradation and segregation/inheritance during cell division.

Peroxisome proliferation in Hansenula polymorpha requires Dnm1p which mediates fission but not de novo formation

We show that the dynamin-like proteins Dnm1p and Vps1p are not required for re-introduction of peroxisomes in Hansenula polymorpha pex3 cells upon complementation with PEX3-GFP. Instead, Dnm1p, but not Vps1p, plays a crucial role in organelle proliferation via fission. In H. polymorpha DNM1 deletion cells (dnm1) a single peroxisome is present that forms long extensions, which protrude into developing buds and divide during cytokinesis. Budding pex11.dnm1 double deletion cells lack these peroxisomal extensions, suggesting that the peroxisomal membrane protein Pex11p is required for their formation. Life cell imaging revealed that fluorescent Dnm1p-GFP spots fluctuate between peroxisomes and mitochondria. On the other hand Pex11p is present over the entire organelle surface, but concentrates during fission at the basis of the organelle extension in dnm1 cells. Our data indicate that peroxisome fission is the major pathway for peroxisome multiplication in H. polymorpha.