Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster E93
Höfundar / Authors: Valgerður J. Hjaltalín (1), Margrét Helga Ögmundsdóttir (1)
Starfsvettvangur / Affiliations: 1. Háskóli Íslands
Kynnir / Presenter: Valgerður J. Hjaltalín
Ubiquitin and ubiquitin-like signaling pathways play diverse roles in eukaryotes. Instead of being anchored to other proteins, the ubiquitin-like protein Atg8, is conjugated to endogenous membranes in a process termed Atg8ylation. This occurs for example during autophagy or related degradative pathways, secretion, and membrane repair. During Atg8ylation, Atg8 is activated by the E1-like enzyme Atg7. This function of Atg7 is highly conserved across eukaryotes. However, we observed that the human protein could not replace its orthologue in Atg7-/- Drosophila melanogaster. Beyond its role in Atg8ylation, several other functions of Atg7 have been described in mammals, such as in metabolism. Interestingly, RNA sequencing revealed a broad effect on metabolic pathways in our Atg7-/- Drosophila. This could indicate that the functions of Atg7 in metabolism are conserved in invertebrates. Previously, we described a shorter isoform of human ATG7, which lacks the Atg8ylation activity. Instead, overexpression of this isoform, which we have termed ATG7(2) as opposed to the canonical ATG7(1), led to suppression of glycolysis and mitochondrial respiration. Interestingly, Drosophila expressing the human ATG7(2) were obese, with the larvae growing double in size, and exhibited other diabetes-like symptoms. This further suggests an Atg8ylation independent function of Atg7 in metabolism through mechanisms conserved from invertebrates to mammals.