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Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation
Jian Luo1,2, Jinzhi Xu1,2, Chaolu Xie1,2
1State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
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.
Insights
Microsporidia parasites hijack host mitochondria, causing fragmentation by altering dynamin 1-like protein (DRP1) phosphorylation. Inhibiting mitochondrial fragmentation reduces parasite replication, revealing a key mechanism for host-pathogen interaction.
Area of Science:
- Cell Biology
- Parasitology
- Mitochondrial Dynamics
Background:
- Microsporidia are obligate intracellular parasites infecting diverse hosts.
- These pathogens manipulate host cell functions, including metabolism and immunity.
- The precise mechanisms of microsporidia-host mitochondria interaction remain largely unknown.
Purpose of the Study:
- To elucidate the mechanism by which microsporidia interact with and manipulate host mitochondria.
- To investigate the role of host mitochondrial fragmentation (HMF) in microsporidian infection.
Main Methods:
- Induction of HMF in host cells infected with microsporidian *Encephalitozoon*.
- Analysis of dynamin 1-like protein (DRP1) phosphorylation status at Ser616 and Ser637.
- Assessment of mitochondrial phosphoglycerate mutase 5 (PGAM5) activation.
- Treatment with mitochondrial division inhibitor 1 (Mdivi1) to evaluate the impact on parasite proliferation.
Main Results:
- Microsporidian *Encephalitozoon* infection significantly induces host mitochondrial fragmentation (HMF).
- Parasites promote DRP1 phosphorylation at Ser616 and dephosphorylation at Ser637 via PGAM5 activation, leading to DRP1 translocation and HMF.
- Inhibition of HMF using Mdivi1 markedly reduces microsporidian replication.
Conclusions:
- Microsporidia actively induce HMF as a strategy to facilitate their replication.
- The study reveals a novel mechanism of host mitochondrial manipulation by microsporidia involving DRP1.
- Findings provide insights into host-pathogen interactions at the mitochondrial level.
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