2022-08-24T00:00:00Z, Deveci, GÖZDE, Kamil, Mohd, Kina, Umit, Temel, Binnur Aydogan, Aly, Ahmed S I, DEVECİ, GÖZDE, KAMIL, MOHD, KINA, ÜMİT YAŞAR, TEMEL, BİNNUR

2022-12-01T00:00:00Z, KAMIL, MOHD, KINA, ÜMİT YAŞAR, DEVECİ, GÖZDE, Akyuz, Sevim N., Yilmaz, Ilknur, ALY, Ahmed Sayed Ibrahım, KAMIL, MOHD, KINA, ÜMİT YAŞAR, DEVECİ, GÖZDE, ALY, AHMED SAYED IBRAHıM

© 2022Positively-charged polyamines are essential molecules for the replication of eukaryotic cells and are particularly important for the rapid proliferation of parasitic protozoa and cancer cells. Unlike in Trypanosoma brucei, the inhibition of the synthesis of intermediate polyamine Putrescine caused only partial defect in malaria parasite blood-stage growth. In contrast, reducing the intracellular concentrations of Spermidine and Spermine by polyamine analogs caused significant defects in blood-stage growth in Plasmodium yoelii and P. falciparum. However, little is known about the synthesizing enzyme of Spermidine and Spermine in the malaria parasite. Herein, malaria parasite conserved Spermidine Synthase (SpdS) gene was targeted for deletion/complementation analyses by knockout/knock-in constructs in P. yoelii. SpdS was found to be essential for blood-stage growth. Live fluorescence imaging in blood-stages and sporozoites confirmed a specific mitochondrial localization, which is not known for any polyamine-synthesizing enzyme so far. This study identifies SpdS as an excellent drug targeting candidate against the malaria parasite, which is localized to the parasite mitochondrion.

2021-09-13T00:00:00Z, Deveci, Gözde, Temel, Binnur, Aly, Ahmed Sayed Ibrahım, DEVECİ, GÖZDE, TEMEL, BİNNUR, ALY, AHMED SAYED IBRAHıM

2024-01-18, Kamil M., KINA Ü. Y., Atmaca H. N., Unal S., Deveci G., Burak P., Aly A. S. I., KAMIL, MOHD, KINA, ÜMİT YAŞAR, DEVECİ, GÖZDE

Endoplasmic reticulum (ER) plays a pivotal role in the regulation of stress responses in multiple eukaryotic cells. However, little is known about the effector mechanisms that regulate stress responses in ER of the malaria parasite. Herein, we aimed to identify the importance of a transmembrane protein 33 (TMEM33)-domain-containing protein in life cycle of the rodent malaria parasite Plasmodium berghei. TMEM33 is an ER membrane-resident protein that is involved in regulating stress responses in various eukaryotic cells. A C-terminal tagged TMEM33 was localized in the ER throughout the blood and mosquito stages of development. Targeted deletion of TMEM33 confirmed its importance for asexual blood stages and ookinete development, in addition to its essential role for sporozoite infectivity in the mammalian host. Pilot scale analysis shows that the loss of TMEM33 results in the initiation of ER stress response and induction of autophagy. Our findings conclude an important role of TMEM33 in the development of all life cycle stages of the malaria parasite, which indicates its potential as an antimalarial target.

2023-01-16, Deveci G., Kamil M., Aly A. S. I., DEVECİ, GÖZDE