BAK proteinaren mekanismo proapoptotikoa aztertzen

Abstract

Apoptosian, proapoptotikoa den BCL2 familiako BAK proteinak mitokondrioko kanpo mintzean (MKM) c-zitokromoaren eta apoptosi-eragileak diren faktoreen (adib. Smac/DIABLO, AIF…) askapenaren erantzule diren poroak eratzen dituela jakina da. Hala ere, BAKen poro apoptotikoaren ezaugarriak eta izaera zeintzuk diren aztertzeke daude. Lan honetan, BAKek c-zitokromoa askatzeaz gain, alofikozianina (104kDa) ere askatzeko adineko poro handiak eratzen dituela ikusi dugu. Gainera, guztiz proteikoak diren kanaletan gertatzen ez den bezala, BAKen poroak tamaina egonkorra eta egitura finkorik ez duela aztertu genuen. Hortaz, BAKek eratzen duen proteinekiko iragazkorra den poroaren tamaina dinamikoa da, izaera proteolipidikoarekin bat eginez.

Current models in apoptosis consider that BCL2 proapoptotic protein BAK forms pores at the mitochondrial outer membrane (MOM) responsible for the release of cytochrome c and other larger apoptotic factors (i.e. Smac/DIABLO, AIF…). However, the properties and nature of BAK apoptotic pore remains enigmatic. Here, we directly visualized that BAK can form membrane pores large enough to release not only cytochrome c, but also allophycocianine (104 kDa). We found that the size of BAK pores is not constant and without any fixed structure, as typically observed in purely proteinaceous channels, demonstrating that BAK forms a protein-permeable pore of dynamic size, in agreement with its proteolipidic nature.