Letter | Published:

ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation

Nature Cell Biology volume 17, pages 689696 (2015) | Download Citation

Abstract

The differentiation of stem cells is a tightly regulated process essential for animal development and tissue homeostasis. Through this process, attainment of new identity and function is achieved by marked changes in cellular properties. Intrinsic cellular mechanisms governing stem cell differentiation remain largely unknown, in part because systematic forward genetic approaches to the problem have not been widely used1,2. Analysing genes required for germline stem cell differentiation in the Drosophila ovary, we find that the mitochondrial ATP synthase plays a critical role in this process. Unexpectedly, the ATP synthesizing function of this complex was not necessary for differentiation, as knockdown of other members of the oxidative phosphorylation system did not disrupt the process. Instead, the ATP synthase acted to promote the maturation of mitochondrial cristae during differentiation through dimerization and specific upregulation of the ATP synthase complex. Taken together, our results suggest that ATP synthase-dependent crista maturation is a key developmental process required for differentiation independent of oxidative phosphorylation.

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Acknowledgements

We thank C. Malone, M. Murphy, J. Carroll, A. Sfeir, E. Skolnik, R. Cinalli, A. Zamparini and A. Blum for comments on the manuscript and advice. We thank F. Liang, C. Petzold and K. Dancel of the NYULMC OCS Microscopy Core for their assistance with transmission electron microscopy, and the NYULMC Immune Monitoring Core supported in part by NCATS NIH grant UL1 TR00038 and NCI NIH grant P30CA016087. We acknowledge the DGRC supported by NIH 2P40OD010949-10A1 and Bloomington Stock Center for reagents. F.K.T. was supported by EMBO and HFSP long-term fellowships, C.G.S. by NIH F31/HD080380, T.R.H. by CIHR, J.R.K.S. by NIH F32/GM082169, B.C. by a PhD fellowship from the Boehringer Ingelheim Fonds and J.B.P. by ACS award 121614-PF-11-277-01-RMC. This work was supported by the NIH (5R01GM062534) and a kind gift from K. W. Davis to G.J.H. G.J.H. is an investigator of the HHMI. R.L. is an HHMI investigator and is supported by NIH R01/R37HD41900.

Author information

Author notes

    • Felipe K. Teixeira
    • , Carlos G. Sanchez
    •  & Thomas R. Hurd

    These authors contributed equally to this work.

    • Jessica R. K. Seifert

    Present address: Department of Biology, Farmingdale State College, State University of New York, Farmingdale, New York 11735, USA.

Affiliations

  1. Howard Hughes Medical Institute (HHMI) and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA

    • Felipe K. Teixeira
    • , Carlos G. Sanchez
    • , Thomas R. Hurd
    • , Jessica R. K. Seifert
    •  & Ruth Lehmann
  2. Watson School of Biological Sciences, HHMI, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

    • Benjamin Czech
    • , Jonathan B. Preall
    •  & Gregory J. Hannon

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Contributions

F.K.T., T.R.H., R.L., C.G.S. and J.R.K.S. designed the experiments. C.G.S. carried out most of the Drosophila crosses, dissections and immunofluorescence stainings. J.R.K.S. and F.K.T. acquired the majority of the confocal microscopy images, with T.R.H. and C.G.S. also contributing. F.K.T. made the dsRNA, carried out the bioinformatics analysis and carried out the RNA expression analysis. T.R.H. carried out the cell culture transfections and CN-PAGE analysis. T.R.H., F.K.T. and R.L. wrote the manuscript, with all authors approving the final version. B.C., J.B.P. and G.J.H. provided the initial list of genes required for oogenesis. R.L., T.R.H., F.K.T., C.G.S. and J.R.K.S. contributed to the discussion of the results.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Thomas R. Hurd or Ruth Lehmann.

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DOI

https://doi.org/10.1038/ncb3165

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