The Drosophila mitochondrial ribosomal protein mRpL12 is required for Cyclin D/Cdk4‐driven growth

The Drosophila melanogaster cyclin‐dependent protein kinase complex CycD/Cdk4 stimulates both cell cycle progression and cell growth (accumulation of mass). CycD/Cdk4 promotes cell cycle progression via the well‐characterized RBF/E2F pathway, but our understanding of how growth is stimulated is still limited. To identify growth regulatory targets of CycD/Cdk4, we performed a loss‐of‐function screen for modifiers of CycD/Cdk4‐induced overgrowth of the Drosophila eye. One mutation that suppressed CycD/Cdk4 was in a gene encoding the mitochondrial ribosomal protein, mRpL12. We show here that mRpL12 is required for CycD/Cdk4‐induced cell growth. Cells homozygous mutant for mRpL12 have reduced mitochondrial activity, and exhibit growth defects that are very similar to those of cdk4 null cells. CycD/Cdk4 stimulates mitochondrial activity, and this is mRpL12 dependent. H if‐1 p rolyl h ydroxylase (Hph), another effector of CycD/Cdk4, regulates growth and is required for inhibition of the hypoxia‐inducible transcription factor 1 (Hif‐1). Both functions depend on mRpL12 dosage, suggesting that CycD/Cdk4, mRpL12 and Hph function together in a common pathway that controls cell growth via affecting mitochondrial activity.