Abstract |
The intracellular parasite Toxoplasma gondii has unique dense granule antigens (GRAs) that are crucial for host infection. Emerging evidence suggests that GRA8 of T. gondii is a promising serodiagnostic marker in toxoplasmosis. However, little is known about the intracellular regulatory mechanisms involved in GRA8-induced host responses. We found that GRA8 interacts with host proteins involved in mitochondria activation and might be useful as a therapeutic strategy for sepsis. Here, we show that protein kinase-Cα (PKCα)-mediated phosphorylation of T. gondii GRA8 (Thr220) is required for mitochondrial trafficking and regulates the interaction of C terminal of GRA8 with nucleotide binding domain of ATP5A1. Furthermore, GRA8 interacts with SIRT3 in mitochondria, facilitating ATP5A1 deacetylation (K506 and K531), adenosine triphosphate production and subsequent anti-septic activity in vivo. Taken together, these results demonstrate a new anti- sepsis therapeutic strategy using T. gondii GRA8-induced mitochondrial metabolic resuscitation. This strategy represents an urgently needed paradigm shift for therapeutic intervention.
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Authors | Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Sojin Kim, Sun Young Kim, Kiseok Jang, Chul-Su Yang |
Journal | Experimental & molecular medicine
(Exp Mol Med)
Vol. 50
Issue 3
Pg. e464
(03 30 2018)
ISSN: 2092-6413 [Electronic] United States |
PMID | 29869623
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Protozoan
- GRA8 protein, Toxoplasma gondii
- Protozoan Proteins
- Sirtuin 3
- Mitochondrial Proton-Translocating ATPases
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Topics |
- Animals
- Antigens, Protozoan
(genetics, metabolism)
- Female
- HEK293 Cells
- Humans
- Mass Spectrometry
- Mice
- Mice, Inbred C57BL
- Mitochondria
(metabolism)
- Mitochondrial Proton-Translocating ATPases
(genetics, metabolism)
- Phosphorylation
- Protein Binding
- Protozoan Proteins
(genetics, metabolism)
- Sepsis
(metabolism)
- Sirtuin 3
(genetics, metabolism)
- Toxoplasmosis
(metabolism)
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