Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation.
Mitochondria, recognized as the "powerhouse" of cells, play a vital role in generating cellular energy through dynamic processes such as fission and fusion. Viruses have evolved mechanisms to hijack mitochondrial function for their survival and proliferation. Here, we report that infection...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012872 |
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| author | Zhe Sun Zicheng Ma Wandi Cao Chenlong Jiang Lei Guo Kesen Liu Yanni Gao Juan Bai Jiang Pi Ping Jiang Xing Liu |
| author_facet | Zhe Sun Zicheng Ma Wandi Cao Chenlong Jiang Lei Guo Kesen Liu Yanni Gao Juan Bai Jiang Pi Ping Jiang Xing Liu |
| author_sort | Zhe Sun |
| collection | DOAJ |
| description | Mitochondria, recognized as the "powerhouse" of cells, play a vital role in generating cellular energy through dynamic processes such as fission and fusion. Viruses have evolved mechanisms to hijack mitochondrial function for their survival and proliferation. Here, we report that infection with the swine arterivirus porcine reproductive and respiratory syndrome virus (PRRSV), manipulates mitochondria calcium ions (Ca2+) to induce mitochondrial fission and mitophagy, thereby reprogramming cellular energy metabolism to facilitate its own replication. Mechanistically, PRRSV-induced mitochondrial fission is caused by elevated levels of mitochondria Ca2+, derived from the endoplasmic reticulum (ER) through inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter (MCU) channels. This process is associated with increased mitochondria-associated membranes (MAMs), mediated by the upregulated expression of sigma non-opioid intracellular receptor 1 (SIGMAR1). Elevated mitochondria Ca2+ further activates the Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-AMP-activated protein kinase (AMPK)-dynamin-related protein 1 (DRP1) signaling pathway, which interacts with mitochondrial fission protein 1 (FIS1) and mitochondrial dynamics proteins of 49 kDa (MiD49) to promote mitochondrial fission. PRRSV infection, alongside mitochondrial fission, triggers mitophagy via the PTEN-induced putative kinase 1 (PINK1)-Parkin RBR E3 ubiquitin (Parkin) pathway, promoting cellular glycolysis and excessive lactate production to facilitate its own replication. This study reveals the mechanism by which mitochondrial Ca2+ regulates mitochondrial function during PRRSV infection, providing new insights into the interplay between the virus and host cell metabolism. |
| format | Article |
| id | doaj-art-274d907c94194ac3bfeb362b8abc7f7c |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-274d907c94194ac3bfeb362b8abc7f7c2025-02-03T21:30:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101287210.1371/journal.ppat.1012872Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation.Zhe SunZicheng MaWandi CaoChenlong JiangLei GuoKesen LiuYanni GaoJuan BaiJiang PiPing JiangXing LiuMitochondria, recognized as the "powerhouse" of cells, play a vital role in generating cellular energy through dynamic processes such as fission and fusion. Viruses have evolved mechanisms to hijack mitochondrial function for their survival and proliferation. Here, we report that infection with the swine arterivirus porcine reproductive and respiratory syndrome virus (PRRSV), manipulates mitochondria calcium ions (Ca2+) to induce mitochondrial fission and mitophagy, thereby reprogramming cellular energy metabolism to facilitate its own replication. Mechanistically, PRRSV-induced mitochondrial fission is caused by elevated levels of mitochondria Ca2+, derived from the endoplasmic reticulum (ER) through inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter (MCU) channels. This process is associated with increased mitochondria-associated membranes (MAMs), mediated by the upregulated expression of sigma non-opioid intracellular receptor 1 (SIGMAR1). Elevated mitochondria Ca2+ further activates the Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-AMP-activated protein kinase (AMPK)-dynamin-related protein 1 (DRP1) signaling pathway, which interacts with mitochondrial fission protein 1 (FIS1) and mitochondrial dynamics proteins of 49 kDa (MiD49) to promote mitochondrial fission. PRRSV infection, alongside mitochondrial fission, triggers mitophagy via the PTEN-induced putative kinase 1 (PINK1)-Parkin RBR E3 ubiquitin (Parkin) pathway, promoting cellular glycolysis and excessive lactate production to facilitate its own replication. This study reveals the mechanism by which mitochondrial Ca2+ regulates mitochondrial function during PRRSV infection, providing new insights into the interplay between the virus and host cell metabolism.https://doi.org/10.1371/journal.ppat.1012872 |
| spellingShingle | Zhe Sun Zicheng Ma Wandi Cao Chenlong Jiang Lei Guo Kesen Liu Yanni Gao Juan Bai Jiang Pi Ping Jiang Xing Liu Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation. PLoS Pathogens |
| title | Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation. |
| title_full | Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation. |
| title_fullStr | Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation. |
| title_full_unstemmed | Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation. |
| title_short | Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation. |
| title_sort | calcium mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation |
| url | https://doi.org/10.1371/journal.ppat.1012872 |
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