Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster
Abstract
Deciphering the systemic signaling mechanisms that modulate metabolic activity has important implications owing to the central role that metabolism plays in regulating organismal adaptability and survival. Here, we show that loss of Drosophila TGF-β/Activin-like ligand Dawdle (Daw) causes major alterations in larval metabolic activity, including accumulation of tricarboxylic acid cycle intermediates, acidification of hemolymph pH, and misregulation of insulin signaling and nuclear-encoded mitochondrial gene expression. These metabolic defects lead to a food-dependent lethality phenotype, suggesting that Daw likely influences environmental adaptability via its modulation of several central metabolic processes. These observations, coupled with previous findings in mammals and Caenorhabditis elegans, highlight a potentially conserved role for TGF-β/Activin signaling in regulating important metabolic processes across the animal kingdom and may have clinical implications.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- April 2014
- DOI:
- 10.1073/pnas.1319116111
- Bibcode:
- 2014PNAS..111.5729G