UNDERAPPRECIATED ROLE OF ATP IN STRESS GRANULE BIOLOGY IN TRYPANOSOMA BRUCEI

Abstract

Autophagy and stress granule (SG) formation are conserved stress response pathways activated by various stresses. In Trypanosoma brucei, autophagy and SGs have been studied individually using different starvation conditions; the former during amino acid starvation, and the latter using conditions deprived of amino acids and carbon sources. Hence, the relationship between autophagy and SG formation has not been investigated.

In this thesis, I established conditions that allow autophagy and SG formation to be studied simultaneously in T. brucei. Inhibition of autophagy reduces SG formation. By including carbon sources for ATP generation during SG formation, I have uncovered various aspects of SG biology modulated by cellular ATP; from formation to dynamicity and dissolution. SGs formed in the presence or absence of carbon sources have different protein compositions; specific protein components associate-dissociate with SGs in response to cellular ATP levels. Liquid-liquid phase separation and liquid-like properties of SGs are also documented.