This weeks Lab Journal Club..Mlx-Mondo transcriptional regulation and sugar tolerance in larvae

This week in JC we discussed a recent paper on high sugar tolerance in larvae from the Hietakangas lab:

Mondo/ChREBP-Mlx-regulated transcriptional network is essential for dietary sugar tolerance in Drosophila. Havula E, Teesalu M, Hyötyläinen T, Seppälä H, Hasygar K, Auvinen P, Orešič M, Sandmann T, Hietakangas V. PLoS Genet. 2013 Apr;9(4):e1003438.

The paper describes how the Mlx-Mondo transcriptional complex is required for larvae to tolerate a high sugar diet –  Mlx mutants can develop to pupae on normal food, but show reduced larval growth and fail to pupate on a high sugar diet. The paper goes on to describe alterations in carbohydrate and lipid metabolism that may account for the high sugar sensitivity in mlx mutants. In particular, two targets of Mondo-Mlx – the transcription factor cabut and the detoxifying enzyme Aldehyde dehydrogenase type III  – are required for high sugar tolerance.

Overall, we liked this paper. We think a lot about how dietary protein can influence larval growth via insulin/TOR signaling. But clearly alterations in dietary sugar, and probably changes in the ratio of sugar: protein, can have important effects on larval physiology and growth.

Questions we had: How do larvae sense and respond to high sugar? via changes in insulin signaling? (see Pasco and Leopold, 2012). Does Mondo-Mlx transcriptional activity respond to changes in diet and/or insulin signaling? (increased expression? increased DNA localization?). Do Mondo-Mlx mutants show altered responses to dietary amino acids and do alterations in the relative balance of dietary sugar: protein influence larval growth?