Líf - og heilbrigðisvísindaráðstefna Háskóla Íslands 2023

The isoform-specific effects of ATG7 on metabolism

Ingvi Karl Jónsson, Margrét Helga Ögmundsdóttir, Óttar Rolfsson

Introduction: Autophagy is a degradative pathway vital for homeostasis. Autophagy plays a complex role in tumorigenesis and tumor progression and suppression. The key autophagy protein ATG7 is required for proper function of the pathway and is crucial for mouse survival. Previous studies have shown that a short isoform of ATG7 does not mediate autophagic function, but interacts with various metabolic proteins. Furthermore, this short isoform has been shown to inhibit glycolysis and mitochondrial activity.
Methods: Mouse embryonic fibroblasts with Atg7 knockout transfected with the characterized ATG7, the short ATG7 isoform or empty vector were used as well as wild-type mouse embryonic fibroblasts. The knockout cells were treated with doxycycline to induce ATG7 isoform expression. The cells were cultured and harvested for metabolomic mass spectrometry sample preparation where metabolites were analyzed by liquid chromatography-mass spectrometry.
Results: Targetted analysis towards sugar metabolism shows altering effects of the short ATG7 isoform on intracellular concentrations of intermediates through glycolysis, the pentose phosphate pathway and the tricarboxylic acid cycle. Results from untargetted analysis indicate further metabolic changes.
Conclusions: The short ATG7 isoform plays a role in sugar metabolism. The results furthermore indicate a potential metabolic role of the short ATG7 isoform outside sugar metabolism, which will help understand the role of autophagy in the metabolic dysregulation of cancers.


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