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.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
ATF4 regulates mitochondrial dysfunction and mitophagy, contributing to corneal endothelial apoptosis
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 21 January 2026

ATF4 regulates mitochondrial dysfunction and mitophagy, contributing to corneal endothelial apoptosis

  • Saba Qureshi1,
  • Stefan Y. Kim1 na1,
  • Stephanie Lee1 na1,
  • Lukas Ritzer1,
  • William Steidl1,
  • Gayle Joliet Krest2,
  • Anisha Kasi1 &
  • …
  • Varun Kumar1,3,4 

Scientific Reports , Article number:  (2026) Cite this article

  • 414 Accesses

  • 5 Altmetric

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cell biology
  • Diseases
  • Molecular biology

Abstract

Endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and mitophagy are known to contribute independently to corneal endothelial cell (CEnC) apoptosis in Fuchs’ endothelial corneal dystrophy (FECD). However, the role of a specific ER stress pathway (PERK-ATF4-CHOP) in regulating these events is unknown. This study aims to investigate the role of ATF4 in regulating mitochondrial dysfunction and mitophagy, which ultimately leads to CEnC apoptosis. Human corneal endothelial cell line (21T), Fuchs’ corneal endothelial cell line (F35T), and primary human corneal endothelial cells were treated with ER stressor tunicamycin (Tun). ATF4 siRNA was used to knock down ATF4 in 21T cell line and primary corneal endothelial cells. Mitophagy and apoptotic proteins were analyzed using Western blotting. ATF4+/− and ATF4 +/+ mice were irradiated with UVA to assess ER stress and corneal endothelial apoptosis. F35T cell line had significantly increased expression of the ER stress pathway as well as caspase-mediated apoptotic molecules compared to 21T at baseline, which further increased after Tun treatment. F35T cells exhibited significantly decreased mitochondrial ATP and MMP, and increased mitochondrial fragmentation, which was further exacerbated after Tun. F35T cells also demonstrated inhibition of mitophagy, similar to 21T, after treatment with tunicamycin, despite the upregulation of mitophagy initiators. ATF4 knockdown attenuated ER and mitochondrial stress proteins, rescued mitochondrial membrane potential (MMP) loss, downregulated mitochondrial fragmentation, activated mitophagy, and prevented CEnC death under chronic ER stress. ATF4+/− mice had increased CE numbers, with improved cellular morphology and decreased ER stress marker CHOP expression, compared to ATF4+/+ mice post-UVA. Pro-apoptotic ATF4 induction following ER stress disrupts mitochondrial function, leading to mitophagy inhibition and CEnC apoptosis. This study highlights the importance of ATF4 in ER-mitochondrial crosstalk and its contribution to CEnC apoptosis in FECD.

Data availability

Data generated in this study will be available from the corresponding author upon request.

References

  1. Krachmer, J. H., Purcell, J. J. Jr., Young, C. W. & Bucher, K. D. Corneal endothelial dystrophy. A study of 64 families. Arch. Ophthalmol. 96, 2036–2039. https://doi.org/10.1001/archopht.1978.03910060424004 (1978).

    Google Scholar 

  2. Poulsen, E. T. et al. Proteomics of fuchs’ endothelial corneal dystrophy support that the extracellular matrix of descemet’s membrane is disordered. J. Proteome Res. 13, 4659–4667. https://doi.org/10.1021/pr500252r (2014).

    Google Scholar 

  3. Benischke, A. S. et al. Activation of mitophagy leads to decline in Mfn2 and loss of mitochondrial mass in Fuchs endothelial corneal dystrophy. Sci. Rep. 7, 6656. https://doi.org/10.1038/s41598-017-06523-2 (2017).

    Google Scholar 

  4. Halilovic, A. et al. Menadione-Induced DNA damage leads to mitochondrial dysfunction and fragmentation during rosette formation in Fuchs endothelial corneal dystrophy. Antioxid. Redox Signal. 24, 1072–1083. https://doi.org/10.1089/ars.2015.6532 (2016).

    Google Scholar 

  5. Okumura, N. et al. Sustained activation of the unfolded protein response induces cell death in fuchs’ endothelial corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 58, 3697–3707. https://doi.org/10.1167/iovs.16-21023 (2017).

    Google Scholar 

  6. Okumura, N. et al. Activation of TGF-beta signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy. Sci. Rep. 7, 6801. https://doi.org/10.1038/s41598-017-06924-3 (2017).

    Google Scholar 

  7. Kaur, S. et al. Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in parkinson’s disease. Life Sci. 330, 121995. https://doi.org/10.1016/j.lfs.2023.121995 (2023).

    Google Scholar 

  8. Naia, L., Ferreira, I. L., Ferreiro, E. & Rego, A. C. Mitochondrial Ca(2+) handling in huntington’s and alzheimer’s diseases - Role of ER-mitochondria crosstalk. Biochem. Biophys. Res. Commun. 483, 1069–1077. https://doi.org/10.1016/j.bbrc.2016.07.122 (2017).

    Google Scholar 

  9. Sakai, S., Watanabe, S., Komine, O., Sobue, A. & Yamanaka, K. Novel reporters of mitochondria-associated membranes (MAM), MAMtrackers, demonstrate MAM disruption as a common pathological feature in amyotrophic lateral sclerosis. FASEB J. 35, e21688. https://doi.org/10.1096/fj.202100137R (2021).

    Google Scholar 

  10. Wang, X., Luo, D. & Wu, S. Molecular Dysfunctions of Mitochondria-Associated Endoplasmic Reticulum Contacts in Atherosclerosis. Oxid Med Cell Longev 2021, 2424509. https://doi.org/10.1155/2021/2424509 (2021).

  11. Qureshi, S. et al. Endoplasmic reticulum stress disrupts mitochondrial Bioenergetics, dynamics and causes corneal endothelial cell apoptosis. Invest. Ophthalmol. Vis. Sci. 64, 18. https://doi.org/10.1167/iovs.64.14.18 (2023).

    Google Scholar 

  12. Neill, G. & Masson, G. R. A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response. Front. Mol. Neurosci. 16, 1112253. https://doi.org/10.3389/fnmol.2023.1112253 (2023).

    Google Scholar 

  13. Pakos-Zebrucka, K. et al. The integrated stress response. EMBO Rep. 17, 1374–1395. https://doi.org/10.15252/embr.201642195 (2016).

    Google Scholar 

  14. Bouman, L. et al. Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell. Death Differ. 18, 769–782. https://doi.org/10.1038/cdd.2010.142 (2011).

    Google Scholar 

  15. Quiros, P. M. et al. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. J. Cell. Biol. 216, 2027–2045. https://doi.org/10.1083/jcb.201702058 (2017).

    Google Scholar 

  16. Dlamini, M. B. et al. The crosstalk between mitochondrial dysfunction and Endoplasmic reticulum stress promoted ATF4-mediated mitophagy induced by hexavalent chromium. Environ. Toxicol. 36, 1162–1172. https://doi.org/10.1002/tox.23115 (2021).

    Google Scholar 

  17. B’Chir, W. et al. The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 41, 7683–7699. https://doi.org/10.1093/nar/gkt563 (2013).

    Google Scholar 

  18. Luhr, M. et al. The kinase PERK and the transcription factor ATF4 play distinct and essential roles in autophagy resulting from tunicamycin-induced ER stress. J. Biol. Chem. 294, 8197–8217. https://doi.org/10.1074/jbc.RA118.002829 (2019).

    Google Scholar 

  19. Hiramatsu, N. et al. Translational and posttranslational regulation of XIAP by eIF2alpha and ATF4 promotes ER stress-induced cell death during the unfolded protein response. Mol. Biol. Cell. 25, 1411–1420. https://doi.org/10.1091/mbc.E13-11-0664 (2014).

    Google Scholar 

  20. Bahamondes Lorca, V. A., Bastidas Mayorga, B. D., Tong, L. & Wu, S. UVB-induced eIF2alpha phosphorylation in keratinocytes depends on decreased ATF4, GADD34 and CReP expression levels. Life Sci. 286, 120044. https://doi.org/10.1016/j.lfs.2021.120044 (2021).

    Google Scholar 

  21. Liu, C. et al. Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected. Proc. Natl. Acad. Sci. U S A. 117, 573–583. https://doi.org/10.1073/pnas.1912546116 (2020).

    Google Scholar 

  22. Schmedt, T. et al. Telomerase immortalization of human corneal endothelial cells yields functional hexagonal monolayers. PLoS One. 7, e51427. https://doi.org/10.1371/journal.pone.0051427 (2012).

    Google Scholar 

  23. Saha, S. et al. TCF4 trinucleotide repeat expansions and UV irradiation increase susceptibility to ferroptosis in Fuchs endothelial corneal dystrophy. Redox Biol. 77, 103348. https://doi.org/10.1016/j.redox.2024.103348 (2024).

    Google Scholar 

  24. Bartakova, A., Kuzmenko, O., Alvarez-Delfin, K., Kunzevitzky, N. J. & Goldberg, J. L. A cell culture approach to optimized human corneal endothelial cell function. Invest. Ophthalmol. Vis. Sci. 59, 1617–1629. https://doi.org/10.1167/iovs.17-23637 (2018).

    Google Scholar 

  25. Liu, H. et al. NARFL deficiency caused mitochondrial dysfunction in lung cancer cells by HIF-1alpha-DNMT1 axis. Sci. Rep. 13, 17176. https://doi.org/10.1038/s41598-023-44418-7 (2023).

    Google Scholar 

  26. Raut, N. A. et al. RNA-Seq Analysis of MCF-7 Breast Cancer Cells Treated with Methyl Gallate Isolated from the Rhizomes of Nymphaea Odorata L. Shows Upregulation of Apoptosis, Autophagy, and Unfolded Protein Canonical Pathways. Molecules 30. https://doi.org/10.3390/molecules30143022 (2025).

  27. Bohm, M. et al. Mitochondria-Targeted antioxidant (MitoQ) and nontargeted antioxidant (Idebenone) mitigate mitochondrial dysfunction in corneal endothelial cells. Cornea 44, 492–503. https://doi.org/10.1097/ICO.0000000000003801 (2025).

    Google Scholar 

  28. Chaudhry, A., Shi, R. & Luciani, D. S. A pipeline for multidimensional confocal analysis of mitochondrial morphology, function, and dynamics in pancreatic beta-cells. Am. J. Physiol. Endocrinol. Metab. 318, E87–E101. https://doi.org/10.1152/ajpendo.00457.2019 (2020).

    Google Scholar 

  29. Rehman, J. et al. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB J. 26, 2175–2186. https://doi.org/10.1096/fj.11-196543 (2012).

    Google Scholar 

  30. Engler, C. et al. Unfolded protein response in Fuchs endothelial corneal dystrophy: a unifying pathogenic pathway? Am. J. Ophthalmol. 149, 194–202e192. https://doi.org/10.1016/j.ajo.2009.09.009 (2010).

    Google Scholar 

  31. Zhao, T. et al. Central role of Mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J. Biol. Chem. 287, 23615–23625. https://doi.org/10.1074/jbc.M112.379164 (2012).

    Google Scholar 

  32. Sebastian, D. et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J. 35, 1677–1693. https://doi.org/10.15252/embj.201593084 (2016).

    Google Scholar 

  33. Fusakio, M. E. et al. Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver. Mol. Biol. Cell. 27, 1536–1551. https://doi.org/10.1091/mbc.E16-01-0039 (2016).

    Google Scholar 

  34. Wu, D. & Liang, J. Activating transcription factor 4: a regulator of stress response in human cancers. Front. Cell. Dev. Biol. 12, 1370012. https://doi.org/10.3389/fcell.2024.1370012 (2024).

    Google Scholar 

  35. Zinszner, H. et al. CHOP is implicated in programmed cell death in response to impaired function of the Endoplasmic reticulum. Genes Dev. 12, 982–995. https://doi.org/10.1101/gad.12.7.982 (1998).

    Google Scholar 

  36. Armstrong, J. L., Flockhart, R., Veal, G. J., Lovat, P. E. & Redfern, C. P. Regulation of Endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells. J. Biol. Chem. 285, 6091–6100. https://doi.org/10.1074/jbc.M109.014092 (2010).

    Google Scholar 

  37. Dekker, P. J. et al. The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44. EMBO J. 16, 5408–5419. https://doi.org/10.1093/emboj/16.17.5408 (1997).

    Google Scholar 

  38. Emtage, J. L. & Jensen, R. E. MAS6 encodes an essential inner membrane component of the yeast mitochondrial protein import pathway. J. Cell. Biol. 122, 1003–1012. https://doi.org/10.1083/jcb.122.5.1003 (1993).

    Google Scholar 

  39. Swerdlow, N. S. & Wilkins, H. M. Mitophagy and the brain. Int. J. Mol. Sci. 21 https://doi.org/10.3390/ijms21249661 (2020).

  40. Oda, T., Kosuge, Y., Arakawa, M., Ishige, K. & Ito, Y. Distinct mechanism of cell death is responsible for tunicamycin-induced ER stress in SK-N-SH and SH-SY5Y cells. Neurosci. Res. 60, 29–39. https://doi.org/10.1016/j.neures.2007.09.005 (2008).

    Google Scholar 

  41. Li, Y. et al. GRP75 Modulates Endoplasmic Reticulum-Mitochondria Coupling and Accelerates Ca(2+)-Dependent Endothelial Cell Apoptosis in Diabetic Retinopathy. Biomolecules 12. https://doi.org/10.3390/biom12121778 (2022).

  42. Ying, Y. et al. Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG. Aging (Albany NY). 13, 8628–8642. https://doi.org/10.18632/aging.202677 (2021).

    Google Scholar 

  43. Kasetti, R. B. et al. ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load. Nat. Commun. 11, 5594. https://doi.org/10.1038/s41467-020-19352-1 (2020).

    Google Scholar 

  44. Fang, F. et al. RGC-specific ATF4 and/or CHOP deletion rescues glaucomatous neurodegeneration and visual function. Mol. Ther. Nucleic Acids. 33, 286–295. https://doi.org/10.1016/j.omtn.2023.07.015 (2023).

    Google Scholar 

  45. Huttemann, M. et al. Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochim. Biophys. Acta. 1817, 598–609. https://doi.org/10.1016/j.bbabio.2011.07.001 (2012).

    Google Scholar 

  46. Saller, B. S. et al. Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation. Immunity 58, 90–107e111. https://doi.org/10.1016/j.immuni.2024.10.012 (2025).

    Google Scholar 

  47. Basak, B. & Holzbaur, E. L. F. Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy. Nat. Commun. 16, 7367. https://doi.org/10.1038/s41467-025-62379-5 (2025).

    Google Scholar 

  48. Miyai, T. et al. Activation of PINK1-Parkin-Mediated mitophagy degrades mitochondrial quality control proteins in Fuchs endothelial corneal dystrophy. Am. J. Pathol. 189, 2061–2076. https://doi.org/10.1016/j.ajpath.2019.06.012 (2019).

    Google Scholar 

  49. Kubli, D. A. et al. PINK1 is dispensable for mitochondrial recruitment of parkin and activation of mitophagy in cardiac myocytes. PLoS One. 10, e0130707. https://doi.org/10.1371/journal.pone.0130707 (2015).

    Google Scholar 

  50. Matus, S., Lopez, E., Valenzuela, V., Nassif, M. & Hetz, C. Functional contribution of the transcription factor ATF4 to the pathogenesis of amyotrophic lateral sclerosis. PLoS One. 8, e66672. https://doi.org/10.1371/journal.pone.0066672 (2013).

    Google Scholar 

  51. Pitale, P. M., Gorbatyuk, O. & Gorbatyuk, M. Neurodegeneration: keeping ATF4 on a tight leash. Front. Cell. Neurosci. 11, 410. https://doi.org/10.3389/fncel.2017.00410 (2017).

    Google Scholar 

  52. Jiang, D. et al. ATF4 mediates mitochondrial unfolded protein response in alveolar epithelial cells. Am. J. Respir Cell. Mol. Biol. 63, 478–489. https://doi.org/10.1165/rcmb.2020-0107OC (2020).

    Google Scholar 

  53. Le, H. T. et al. eIF2alpha phosphorylation-ATF4 axis-mediated transcriptional reprogramming mitigates mitochondrial impairment during ER stress. Mol. Cells. 48, 100176. https://doi.org/10.1016/j.mocell.2024.100176 (2025).

    Google Scholar 

Download references

Acknowledgements

We sincerely thank Allison Sowa, Bill Janssen for electron microscopy processing and imaging at The Microscopy CoRE, Icahn School of Medicine at Mount Sinai. We also thank Ula V. Jurkunas (Schepens Eye Research Institute, Harvard University) for providing HCEnC-21T cell line and Albert Jun (Wilmer Eye Institute, John Hopkins University) for providing F35T cell line.

Funding

Supported by NIH/NEI (R00EY031339), Mount Sinai Seed Money, New York Eye and Ear Foundation, Sarah K de Coizart Charitable Trust/Foundation awarded to V.K. and Challenge Grant from Research to Prevent Blindness awarded to ophthalmology department.

Author information

Author notes

  1. Stefan Y. Kim and Stephanie Lee contributed equally to this work.

Authors and Affiliations

  1. Eye and Vision Research Institute, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Saba Qureshi, Stefan Y. Kim, Stephanie Lee, Lukas Ritzer, William Steidl, Anisha Kasi & Varun Kumar

  2. Columbia University, New York, USA

    Gayle Joliet Krest

  3. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Varun Kumar

  4. Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA

    Varun Kumar

Authors
  1. Saba Qureshi
    View author publications

    Search author on:PubMed Google Scholar

  2. Stefan Y. Kim
    View author publications

    Search author on:PubMed Google Scholar

  3. Stephanie Lee
    View author publications

    Search author on:PubMed Google Scholar

  4. Lukas Ritzer
    View author publications

    Search author on:PubMed Google Scholar

  5. William Steidl
    View author publications

    Search author on:PubMed Google Scholar

  6. Gayle Joliet Krest
    View author publications

    Search author on:PubMed Google Scholar

  7. Anisha Kasi
    View author publications

    Search author on:PubMed Google Scholar

  8. Varun Kumar
    View author publications

    Search author on:PubMed Google Scholar

Contributions

SQ and VK performed experiments, analyzed data, wrote, and revised the manuscript. SYK, SL, LR, WS, GJK, and AK performed experiments and analyzed the data. VK is responsible for all the funding of the lab.

Corresponding author

Correspondence to Varun Kumar.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qureshi, S., Kim, S.Y., Lee, S. et al. ATF4 regulates mitochondrial dysfunction and mitophagy, contributing to corneal endothelial apoptosis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36453-x

Download citation

  • Received: 02 October 2025

  • Accepted: 13 January 2026

  • Published: 21 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-36453-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • ATF4
  • Mitochondrial stress
  • Mitophagy
  • ER stress
  • Cell survival
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

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