Expression profiling of attenuated mitochondrial function identifies retrograde signals in Drosophila.
Mitochondria are able to modulate cell state and fate during normal and pathophysiologic conditions through a nuclear-mediated mechanism collectively termed as a retrograde response. Our previous studies in Drosophila melanogaster have clearly established that progress through the cell cycle is precisely regulated by the intrinsic activity of the mitochondrion by specific signaling cascades mounted by the cell. As a means to further our understanding of how mitochondrial energy status affects nuclear control of basic cell decisions, we have employed Affymetrix microarray-based transcriptional profiling of Drosophila S2 cells knocked down for the gene encoding subunit Va of the complex IV of the mitochondrial electron transport chain. The profiling data identify transcriptional upregulation of glycolytic genes, and metabolic studies confirm this increase in glycolysis. The data provide a model of the shift of metabolism from a predominately oxidative state toward a predominately aerobic glycolytic state mediated through transcriptional control. The transcriptional changes alter many signaling systems, including p53, insulin, hypoxia-induced factor α, and conserved mitochondrial retrograde responses. This rich dataset provides many novel targets for further understanding the mechanism whereby the mitochondrion manages energy substrate disposition and directs cellular fate decisions.
Department of Molecular, Cell, and Developmental Biology, University of California-Los Angeles, CA 90095, USA.
William A
WA
Freije
Sudip
S
Mandal
Utpal
U
Banerjee
D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D029721:Drosophila Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D021122:Protein Subunits; D016159:Tumor Suppressor Protein p53; D003576:Electron Transport Complex IV