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  • The EMBO Journal (2005) 24, 623 - 634
  • doi:10.1038/sj.emboj.7600523

Published online: 3 February 2005

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

Christian Frei1,2, Mireille Galloni3, Ernst Hafen2 and Bruce A Edgar1

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  2. Zoologisches Institut, Universität Zürich, Zürich, Switzerland
  3. INSERM-UM2 E343, Université de Montpellier 2, Montpellier, France

Correspondence to:

Christian Frei, Institute of Cell Biology, HPM F39, ETH Hönggerberg, 8093 Zürich, Switzerland. Tel.: +41 1 633 3447; Fax: +41 1 633 1286; E-mail: christian.frei@zool.unizh.ch

Bruce A Edgar, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Tel.: +1 206 667 4185; Fax: +1 206 3308; E-mail: bedgar@fhcrc.org

Received 14 June 2004; Accepted 25 November 2004

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. Hif-1 prolyl hydroxylase (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.

  • Keywords:

    • Cyclin D/Cdk4,
    • Drosophila,
    • growth,
    • Hif prolyl hydroxylase,
    • mitochondria