Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation

Luo, Jian; Xu, Jinzhi; Xie, Chaolu; Zhao, Zuoming; Guo, Junrui; Wen, Yuan; Li, Tian; Zhou, Zeyang

doi:10.3390/ijms23147746

Open AccessArticle

Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation

by

Jian Luo

^1,2,

Jinzhi Xu

^1,2,

Chaolu Xie

^1,2,

Zuoming Zhao

^1,2,

Junrui Guo

^1,2,

Yuan Wen

^1,2,

Tian Li

^1,2,*

and

Zeyang Zhou

^1,2,3,*

¹

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China

²

Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, China

³

College of Life Science, Chongqing Normal University, Chongqing 400047, China

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(14), 7746; https://doi.org/10.3390/ijms23147746

Submission received: 9 June 2022 / Revised: 8 July 2022 / Accepted: 12 July 2022 / Published: 13 July 2022

(This article belongs to the Section Molecular Immunology)

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Abstract

Microsporidia are obligate intracellular parasites that infect a wide variety of hosts ranging from invertebrates to vertebrates. These parasites have evolved strategies to directly hijack host mitochondria for manipulating host metabolism and immunity. However, the mechanism of microsporidia interacting with host mitochondria is unclear. In the present study, we show that microsporidian Encephalitozoon greatly induce host mitochondrial fragmentation (HMF) in multiple cells. We then reveal that the parasites promote the phosphorylation of dynamin 1-like protein (DRP1) at the 616th serine (Ser616), and dephosphorylation of the 637th serine (Ser637) by highly activating mitochondrial phosphoglycerate mutase 5 (PGAM5). These phosphorylation modifications result in the translocation of DRP1 from cytosol to the mitochondrial outer membrane, and finally lead to HMF. Furthermore, treatment with mitochondrial division inhibitor 1 (Mdivi1) significantly reduced microsporidian proliferation, indicating that the HMF are crucial for microsporidian replication. In summary, our findings reveal the mechanism that microsporidia manipulate HMF and provide references for further understanding the interactions between these ubiquitous pathogens with host mitochondria.

Keywords: microsporidia; mitochondrial fragmentation; DRP1; PGAM5; host–pathogen interaction

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MDPI and ACS Style

Luo, J.; Xu, J.; Xie, C.; Zhao, Z.; Guo, J.; Wen, Y.; Li, T.; Zhou, Z. Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation. Int. J. Mol. Sci. 2022, 23, 7746. https://doi.org/10.3390/ijms23147746

AMA Style

Luo J, Xu J, Xie C, Zhao Z, Guo J, Wen Y, Li T, Zhou Z. Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation. International Journal of Molecular Sciences. 2022; 23(14):7746. https://doi.org/10.3390/ijms23147746

Chicago/Turabian Style

Luo, Jian, Jinzhi Xu, Chaolu Xie, Zuoming Zhao, Junrui Guo, Yuan Wen, Tian Li, and Zeyang Zhou. 2022. "Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation" International Journal of Molecular Sciences 23, no. 14: 7746. https://doi.org/10.3390/ijms23147746

APA Style

Luo, J., Xu, J., Xie, C., Zhao, Z., Guo, J., Wen, Y., Li, T., & Zhou, Z. (2022). Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation. International Journal of Molecular Sciences, 23(14), 7746. https://doi.org/10.3390/ijms23147746

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Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation

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