(original) (raw)

TY - JOUR AU - Owusu-Ansah, Edward AU - Yavari, Amir AU - Mandal, Sudip AU - Banerjee, Utpal PY - 2008 DA - 2008/03/01 TI - Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint JO - Nature Genetics SP - 356 EP - 361 VL - 40 IS - 3 AB - 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. SN - 1546-1718 UR - https://doi.org/10.1038/ng.2007.50 DO - 10.1038/ng.2007.50 ID - Owusu-Ansah2008 ER -