JNK protects Drosophila from oxidative stress by trancriptionally activating autophagy.
JNK signaling functions to induce defense mechanisms that protect organisms against acute oxidative and xenobiotic insults. Using Drosophila as a model system, we investigated the role of autophagy as such a JNK-regulated protective mechanism. We show that oxidative stress can induce autophagy in the intestinal epithelium by a mechanism that requires JNK signaling. Consistently, artificial activation of JNK in the gut gives rise to an autophagy phenotype. JNK signaling can induce the expression of several autophagy-related (ATG) genes, and the integrity of these genes is required for the stress protective function of the JNK pathway. In contrast to autophagy induced by oxidative stress, non-stress related autophagy, as it occurs for example in starving adipose or intestinal tissue, or during metamorphosis, proceeds independently of JNK signaling. Autophagy thus emerges as a multifunctional process that organisms employ in a variety of different situations using separate regulatory mechanisms.
Wu
Hai
H
Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Wang
Meng C
MC
Bohmann
Dirk
D
D000818:Animals; D001343:Autophagy; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism; D006720:Homozygote; D048670:MAP Kinase Kinase 4 / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D048670:MAP Kinase Kinase 4