Letter abstract
Nature Genetics 40, 356 - 361 (2008)
Published online: 3 February 2008 | doi:10.1038/ng.2007.50
Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint
Edward Owusu-Ansah1, Amir Yavari1, Sudip Mandal1 & Utpal Banerjee1,2,3
During electron transport, the mitochondrion generates ATP and reactive oxygen species (ROS), a group of partially reduced and highly reactive metabolites of oxygen1. In this in vivo genetic analysis in Drosophila melanogaster, we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle during the G1-S transition. The mechanism involves a specific signaling cascade initiated by ROS and transduced by ASK-1, JNK, FOXO and the Drosophila p27 homolog, Dacapo. On the basis of our data combined with previous analyses of the system2, we conclude that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. One such signal involves an increase in AMP production and downregulation of cyclin E protein; another independent pathway involves increased ROS and upregulation of Dacapo. Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression.
- Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
- Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095, USA.
- Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California 90095, USA.
Correspondence to: Utpal Banerjee1,2,3 e-mail: banerjee@mbi.ucla.edu
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