Nothing Special   »   [go: up one dir, main page]
Skip to main content

Thank you for visiting nature.com. 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.

  • Comment
  • Published:

Hypermetabolism and energetic constraints in mitochondrial disorders

Nature Metabolism volume 6, pages 192–195 (2024)Cite this article

Subjects

The prevailing notion that mitochondrial diseases arise from ATP deficiency is challenged by recent evidence that oxidative phosphorylation defects trigger maladaptive stress responses consuming excess energy. We argue that this chronic state of hypermetabolism imposes energetic constraints, thus causing mitochondrial disease pathophysiology, calling for careful translational studies from organelle to organism.

Access through your institution
Buy or subscribe

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

Relevant articles

Open Access articles citing this article.

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Proposed model of mitochondrial diseases pathophysiology centred on the (hyper)metabolic phenotype of clinical and pre-clinical models of mitochondrial OxPhos defects.

References

  1. Argov, Z., Bank, W. J., Maris, J., Peterson, P. & Chance, B. Neurology 37, 257–262 (1987).

    Article  PubMed  CAS  Google Scholar 

  2. Sturm, G. et al. Commun. Biol. 6, 22 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Taivassalo, T. et al. Brain 126, 413–423 (2003).

    Article  PubMed  Google Scholar 

  4. Sharma, R. et al. J. Clin. Invest. 131, e136055 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Sercel, A. J. et al. Preprint at bioRxiv https://doi.org/10.1101/2023.09.09.556754 (2023).

  6. Desdín-Micó, G. et al. Science 368, 1371–1376 (2020).

    Article  ADS  PubMed  Google Scholar 

  7. Forsström, S. et al. Cell Metab. 30, 1040–1054.e7 (2019).

    Article  PubMed  Google Scholar 

  8. Ost, M. et al. EMBO Rep. 21, e48804 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Losa, J. et al. Mol. Syst. Biol. 18, e10822 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Barends, M. et al. JIMD Rep. 26, 103–113 (2016).

    Article  PubMed  Google Scholar 

  11. Bobba-Alves, N., Juster, R. P. & Picard, M. Psychoneuroendocrinology 146, 105951 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Speakman, J. R. et al. Cell Rep. Med. 2, 100203 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Desousa, B. R. et al. EMBO Rep. 24, e56380 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Crosswell, A. D. et al. Psychol. Rev. https://doi.org/10.1037/rev0000453 (2023).

    Article  PubMed  Google Scholar 

  15. Naviaux, R. K. Mitochondrion 70, 131–163 (2023).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Work of the authors is partly supported by NIH grants P30-DK26687 to D.G., R35HL155670 and R01HL142648 to M.P.S.O., R01MH122706, R01AG066828, R01MH119336, the Wharton Fund, and the Baszucki Brain Research Fund to M.P.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, USA

    Alexander J. Sercel, Gabriel Sturm & Martin Picard

  2. Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA

    Gabriel Sturm

  3. Department of Medicine, Columbia University Irving Medical Center, New York, USA

    Dympna Gallagher

  4. Division of General Medicine and Center of Excellence for Sleep & Circadian Research, Department of Medicine, Columbia University Irving Medical Center, New York, USA

    Marie-Pierre St-Onge

  5. The Santa Fe Institute, New Mexico, USA

    Christopher P. Kempes

  6. Department of Evolutionary Anthropology, Duke University, North Carolina, USA

    Herman Pontzer

  7. Duke Global Health Institute, Duke University, North Carolina, USA

    Herman Pontzer

  8. Department of Neurology, H. Houston Merritt Center, Columbia University Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, USA

    Michio Hirano & Martin Picard

  9. New York State Psychiatric Institute, New York, USA

    Martin Picard

  10. Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA

    Martin Picard

Authors
  1. Alexander J. Sercel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriel Sturm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dympna Gallagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie-Pierre St-Onge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher P. Kempes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Herman Pontzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michio Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martin Picard
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.J.S. and M.P. conceived the model and prepared the manuscript. G.S., D.G., M.P.S.O., C.P.K., H.P. and M.H. made substantial conceptual and editorial contributions to the final article.

Corresponding author

Correspondence to Martin Picard.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sercel, A.J., Sturm, G., Gallagher, D. et al. Hypermetabolism and energetic constraints in mitochondrial disorders. Nat Metab 6, 192–195 (2024). https://doi.org/10.1038/s42255-023-00968-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42255-023-00968-8

Search

Advanced search

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