Poster Presentation 24th Annual Lorne Proteomics Symposium 2019

The role and regulation of Atg1 in autophagy and DIF-1 induced autophagic cell death of Dictyostelium discoideum (#135)

Melodi G Sen 1 , Sarah J Annesley 1 , Paul R Fisher 1
  1. La trobe University, Bundoora, VIC, Australia

Autophagy is a central process for the maintenance of cell homeostasis and survival of mitochondrially diseased cells. It is a basally active, catabolic process, targeting cytosolic macromolecules and organelles that are unnecessary or dysfunctional. These are degraded and recycled through the activity of lysosomal enzymes. In neurodegenerative and mitochondrial diseases, cells upregulate autophagy in a bid to remove protein aggregates and damaged organelles. After a point of no return, this process results in autophagic cell death. The presence of apoptotic machinery in mammalian cells obscures the study of autophagy in relation to complex diseases. Therefore, the social amoeba, Dictyostelium discoideum, provides a simple model which lacks these apoptotic genes. Furthermore, D. discoideum has homologues for autophagy proteins, which makes it an ideal candidate for this research. Autophagic pathways are crucial for the multicellular development of D. discoideum, as cells targeted for differentiation into stalk cells undergo autophagic cell death. An important regulator of this process is AMP-activated protein kinase (AMPK), which plays a central role in cellular processes such as growth, cell cycle progression and photosensory signal transduction. Downstream of AMPK lies TOR complex 1 (TORC1), which inhibits autophagy, and stimulates cell growth and proliferation. The regulatory activity of TORC1 on autophagy has been found to occur through the ULK1 complex in mammalian cells. In D. discoideum, the role of the ULK1 counterpart, Atg1, has yet to be elucidated. Therefore, this project aims to characterise the role of Atg1 and determine the cellular processes effected by altered expression of Atg1. Furthermore, a thorough understanding of the interactions between Atg1, TORC1 and AMPK in the regulation of autophagic cell death, could provide future targets for therapeutics. Preliminary data suggests which proteins are upregulated or downregulated with a change in Atg1 expression. Furthermore, Atg1 has proven to be essential for normal aggregation, stalk cell differentiation and fruiting body formation in D. discoideum. This suggests that Atg1 is crucial for long term viability of the organism.