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Article

DDIT3 Promotes Starvation-Induced Autophagy via ER Stress in Vero Cells

1
Ministry of Education Engineering Research Centre for Key Technology and Industrialisation of Cell-Based Vaccines, Northwest Minzu University, Lanzhou 730030, China
2
Gansu Tech Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China
3
Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China
4
Gansu Provincial Bioengineering Materials Engineering Research Center, Lanzhou 730010, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2026, 27(10), 4315; https://doi.org/10.3390/ijms27104315
Submission received: 4 March 2026 / Revised: 21 April 2026 / Accepted: 24 April 2026 / Published: 12 May 2026
(This article belongs to the Section Molecular Biology)

Abstract

Vero cells in high-density vaccine cultures often face nutrient starvation, especially in suspension-adapted Vero cells. Previous studies showed that serum starvation dramatically enhances autophagy and mitophagy in suspension-adapted Vero cells. Transcriptomic profiling also revealed significant upregulation of DDIT3, a marker of endoplasmic reticulum stress (ERS), in suspension-adapted Vero cells compared to adherent cells. To investigate the functional role of DDIT3, an Earle’s Balanced Salt Solution (EBSS)-induced starvation model was established in adherent Vero cells, recapitulating key autophagy and ER stress responses observed under suspension conditions. The genetic silencing of DDIT3 by shRNA attenuated autophagy, as evidenced by a reduced LC3-II/LC3-I ratio and impaired autophagosome–lysosome activity. Notably, DDIT3 knockdown enhanced cell proliferation and increased the yield of H1N1 influenza virus under nutrient-deprived conditions. Collectively, these results suggest that DDIT3 may serve as a critical regulator linking ER stress to autophagy in Vero cells, and that the suppression of DDIT3 may represent a promising strategy for developing autophagy-resistant Vero cell lines suitable for high-density suspension culture in vaccine production.
Keywords: Vero cells; DDIT3; autophagy; endoplasmic reticulum stress (ERs) Vero cells; DDIT3; autophagy; endoplasmic reticulum stress (ERs)

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MDPI and ACS Style

Li, M.; Jia, R.; Huang, R.; Wang, J.; Qiao, Z.; Sun, N. DDIT3 Promotes Starvation-Induced Autophagy via ER Stress in Vero Cells. Int. J. Mol. Sci. 2026, 27, 4315. https://doi.org/10.3390/ijms27104315

AMA Style

Li M, Jia R, Huang R, Wang J, Qiao Z, Sun N. DDIT3 Promotes Starvation-Induced Autophagy via ER Stress in Vero Cells. International Journal of Molecular Sciences. 2026; 27(10):4315. https://doi.org/10.3390/ijms27104315

Chicago/Turabian Style

Li, Muzi, Renhou Jia, Rong Huang, Jiamin Wang, Zilin Qiao, and Na Sun. 2026. "DDIT3 Promotes Starvation-Induced Autophagy via ER Stress in Vero Cells" International Journal of Molecular Sciences 27, no. 10: 4315. https://doi.org/10.3390/ijms27104315

APA Style

Li, M., Jia, R., Huang, R., Wang, J., Qiao, Z., & Sun, N. (2026). DDIT3 Promotes Starvation-Induced Autophagy via ER Stress in Vero Cells. International Journal of Molecular Sciences, 27(10), 4315. https://doi.org/10.3390/ijms27104315

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