PhD Public Seminar - Taoyingnan Li

Macroautophagy is a highly conserved catabolic process in eukaryotes in which cellular components such as mitochondria, protein aggregates and invaded pathogens are sequestered into autophagosomes for lysosomal degradation. My lab applied biotin identification (BioID) to known autophagy-related (ATG) proteins and identified IRGQ as a novel interactor of the ATG8 family, members of which are ubiquitin-like proteins required for autophagosome formation. IRGQ belongs to the immunity-related GTPase family, which are interferon-inducible resistance factors against several intracellular pathogens such as Toxoplasma gondii. IRGQ is highly conserved in mammals, but its function remains unknown. I showed that IRGQ interacts most strongly with the ATG8 family member GABARAPL2 and the remainder of the ATG8 family through different ATG8 family-interacting motifs (AIMs). Although having strong interactions with multiple ATG8s, I showed that IRGQ doesn’t regulate basal and starvation-induced autophagosome formation and three types of selective autophagy: xenophagy (Salmonella), aggrephagy (protein aggregates) and mitophagy (mitochondria). Furthermore, I examined the role of IRGQ in autophagy-independent functions of ATG8s and found that IRGQ is an exosomal cargo and may impact the composition of exosomes. Next, I investigated the role of IRGQ in vivo using Irgq-/- mice. I tested the role of IRGQ in anti-bacterial immunity by using two infection models: Listeria monocytogenes and Citrobacter rodentium and found that Irgq-/- male mice have normal resistance to these two bacteria. However, I discovered that Irgq-/- female mice have reduced fertility caused by defective activation of ovarian follicles accompanied by delayed clearance of corpus luteum. Furthermore, Irgq-/- male mice also display deficiencies in fear learning and memory. Thus, Irgq may play important roles in animal behavior and female fertility that are worthy of future investigation. Taken together, my work is the first systemic study to characterize the functions of IRGQ both in vitro and in vivo.