RRC ID 53498
Author Moreno-Arriola E, El Hafidi M, Ortega-Cuéllar D, Carvajal K.
Title AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators.
Journal PLoS One
Abstract Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases.
Volume 11(1)
Pages e0148089
Published 2016-1-1
DOI 10.1371/journal.pone.0148089
PII PONE-D-15-24271
PMID 26824904
PMC PMC4732773
MeSH AMP-Activated Protein Kinases Aminoimidazole Carboxamide / analogs & derivatives Aminoimidazole Carboxamide / pharmacology Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Respiration / drug effects Energy Metabolism / drug effects Energy Metabolism / genetics Fatty Acids / metabolism Gene Expression Regulation Glucose / metabolism Humans Lactic Acid / metabolism Longevity / genetics Metformin / pharmacology Mitochondria / drug effects Mitochondria / metabolism Oxygen / metabolism Oxygen Consumption / drug effects Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Protein Subunits / genetics* Protein Subunits / metabolism Receptors, Cytoplasmic and Nuclear / genetics* Receptors, Cytoplasmic and Nuclear / metabolism Ribonucleotides / pharmacology Signal Transduction Transcription Factors / genetics* Transcription Factors / metabolism Transcription, Genetic
IF 2.74
Times Cited 21
C.elegans tm2182