Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy


We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. Our results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Positional cloning of TMEM70.
Figure 2: TMEM70 complementation of ATP synthase deficiency.


  1. Collinson, I.R., Skehel, J.M., Fearnley, I.M., Runswick, M.J. & Walker, J.E. Biochemistry 35, 12640–12646 (1996).

    Article  CAS  Google Scholar 

  2. Ackerman, S.H. & Tzagoloff, A. Prog. Nucleic Acid Res. Mol. Biol. 80, 95–133 (2005).

    Article  CAS  Google Scholar 

  3. Pickova, A., Potocky, M. & Houstek, J. Proteins 59, 393–402 (2005).

    Article  CAS  Google Scholar 

  4. Wang, Z.G., White, P.S. & Ackerman, S.H. J. Biol. Chem. 276, 30773–30778 (2001).

    Article  CAS  Google Scholar 

  5. Zeng, X., Neupert, W. & Tzagoloff, A. Mol. Biol. Cell 18, 617–626 (2007).

    Article  CAS  Google Scholar 

  6. Houstek, J. et al. Biochim. Biophys. Acta 1757, 1400–1405 (2006).

    Article  CAS  Google Scholar 

  7. Schon, E.A., Santra, S., Pallotti, F. & Girvin, M.E. Semin. Cell Dev. Biol. 12, 441–448 (2001).

    Article  CAS  Google Scholar 

  8. Jonckheere, A. et al. J. Med. Genet. 45, 129–133 (2007).

    Article  Google Scholar 

  9. Houstek, J. et al. Hum. Mol. Genet. 8, 1967–1974 (1999).

    Article  CAS  Google Scholar 

  10. Sperl, W. et al. Neuromuscul. Disord. 16, 821–829 (2006).

    Article  CAS  Google Scholar 

  11. De Meirleir, L. et al. J. Med. Genet. 41, 120–124 (2004).

    Article  CAS  Google Scholar 

  12. Mayr, J.A. et al. Pediatr. Res. 55, 988–994 (2004).

    Article  CAS  Google Scholar 

  13. Cizkova, A. et al. BMC Genomics 9, 38 (2008).

    Article  Google Scholar 

  14. Calvo, S. et al. Nat. Genet. 38, 576–582 (2006).

    Article  CAS  Google Scholar 

Download references


This study was supported by grants from Ministry of Education of Czech Republic (1M6837805002, AV0Z 50110509, MSM0021620806, Kontakt 14/2006), GAČR (305/08/H037), OeNB 12568, Päd. Forschungsverein and PMU Salzburg (06/04/022). We thank R.Gallyová, Š.Rosipal, V.Smolka, A.Hlavatá, P.Freisinger, M.Huemer and O.Bodamer, who provided samples from affected individuals for this study, and D. Seelow for bioinformatic support.

Author information

Authors and Affiliations



A.C., H.Hartmannová and L.N. carried out DNA and gene expression analysis and TMEM70 cloning. V.S. and R.I. were responsible for genotyping, gene expression analysis and bioinformatics. J.A.M. carried out biochemical diagnosis and DNA analysis. A.W.K. did genotyping and homozygosity mapping. M.T. and H.Hansíková carried out biochemical diagnosis, cell culturing and transfections. V.H., J.P. and V.K. carried out transfections, complementation studies, ELFO/WB analysis and bioinformatics. M.V., Z.D. and K.H. were responsible for functional studies. T.H. and M.M. were responsible for family ascertainment and sample collection, and J.Z. and W.S. handled diagnosis and clinical characterization. S.K. and J.H. initiated and coordinated the study and wrote the manuscript.

Corresponding authors

Correspondence to Josef Houštěk or Stanislav Kmoch.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Tables 1 and 2, Supplementary Methods (PDF 272 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Čížková, A., Stránecký, V., Mayr, J. et al. TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. Nat Genet 40, 1288–1290 (2008).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing