Mitochondrial dysfunction has been implicated in much human pathology, including cancer, and may be involved in aging. We have used the model organism, Drosophila melanogaster, to examine the metabolic, mitochondrial, and aging consequences of a common oncogene, Cyclin D (CycD). The cyclin dependent protein kinase complex CycD/Cdk4 has been shown to regulate both cellular growth (accumulation of mass) as well as proliferation (cell cycle progression) in Drosophila melanogaster. These two roles of Drosophila CycD/Cdk4 seem to be separable, with the proliferative function acting thru the phosphorylation-dependent inhibition of Rb (retinoblastoma) protein, and the growth effects mediated through a mitochondrial ribosomal protein (mRpL12), and a hydoxylase enzyme involved in mediating cellular responses to oxygen (Hph). In mammalian cells, excess CycD1 activity has been shown to cooperate with several other oncogenes, and promotes tumorgenesis. CycD1's tumorigenic function has been ascribed to the inhibition of Rb (tumor suppressor) protein, although mammalian CycD1 also regulates transcriptional pathways involved in metabolism of carbohydrates, lipids, amino acids, and other substrates. We have found that in Drosophila, the increased activity of CycD/Cdk4 leads to increased mitochondrial biogenesis and Tfam, the major mitochondrial transcription factor. Systemic CycD/Cdk4 also decreases lifespan and increases mitochondrial superoxide, perhaps a side effect of the increased mitochondrial numbers or metabolism. Pan-neuronally expressed CycD/Cdk4 replicated the lifespan reduction phenotype, indicating that neuronal tissues may be the most sensitive to the oxidative stress induced by CycD/Cdk4 activity. We also find that excess CycD/Cdk4 sensitized animals to hypoxic stress (lowered O₂), suggesting its involvement in cellular metabolism as a function of oxygen levels. We find that the knockdown of Tfam or NRF-1 (with RNAi) can, in part, abrogate CycD/Cdk4's detrimental effects on both lifespan and hypoxic sensitization, implying that CycD/Cdk4's pathological consequences are mediated through its promotion of mitochondrial biogenesis or the concomitant increase in reactive oxygen species (ROS). This introduces the possibility that unregulated CycD/Cdk4 activity leading to increased mitochondrial biogenesis and/or amplified ROS may contribute to tumorgenesis.