Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference
PE_PGRS30 belongs to the PE_PGRS protein family and is characterized by a conserved Pro-Glu (PE) domain and a typically polymorphic GC-rich sequence (PGRS) domain. PE_PGRS30 is a virulence factor of Mycobacterium tuberculosis that induces macrophage cell death. We found that RAW264.7 cells and murin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1080369/full |
| _version_ | 1811176992845856768 |
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| author | Kazunori Matsumura Satoshi Takaki Teruo Kirikae |
| author_facet | Kazunori Matsumura Satoshi Takaki Teruo Kirikae |
| author_sort | Kazunori Matsumura |
| collection | DOAJ |
| description | PE_PGRS30 belongs to the PE_PGRS protein family and is characterized by a conserved Pro-Glu (PE) domain and a typically polymorphic GC-rich sequence (PGRS) domain. PE_PGRS30 is a virulence factor of Mycobacterium tuberculosis that induces macrophage cell death. We found that RAW264.7 cells and murine alveolar macrophages underwent apoptosis in response to PE_PGRS30. The host protein prohibitin 2 (PHB2) was identified as a target molecule. PE_PGRS30 and PHB2 interact via the PGRS domain and mitochondrial targeting sequence, respectively. PHB2 overexpression reduced macrophage apoptosis in response to PE_PGRS30. PE_PGRS30 co-localized with PHB2, not in mitochondria, but in lysosomes. The maintenance of mitochondrial structure by PHB2 was impaired in response to the PGRS domain. These results indicated that PE_PGRS30 reduces PHB2 in mitochondria, resulting in mitochondrial dysfunction and cellular apoptosis. |
| first_indexed | 2024-04-10T20:01:02Z |
| format | Article |
| id | doaj.art-09c08a4da36b457cb6238aa5bce29578 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-10T20:01:02Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-09c08a4da36b457cb6238aa5bce295782023-01-27T04:47:29ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-01-011410.3389/fmicb.2023.10803691080369Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interferenceKazunori Matsumura0Satoshi Takaki1Teruo Kirikae2Department of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Chiba, JapanDepartment of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Chiba, JapanGraduate School of Medicine, Juntendo University, Tokyo, JapanPE_PGRS30 belongs to the PE_PGRS protein family and is characterized by a conserved Pro-Glu (PE) domain and a typically polymorphic GC-rich sequence (PGRS) domain. PE_PGRS30 is a virulence factor of Mycobacterium tuberculosis that induces macrophage cell death. We found that RAW264.7 cells and murine alveolar macrophages underwent apoptosis in response to PE_PGRS30. The host protein prohibitin 2 (PHB2) was identified as a target molecule. PE_PGRS30 and PHB2 interact via the PGRS domain and mitochondrial targeting sequence, respectively. PHB2 overexpression reduced macrophage apoptosis in response to PE_PGRS30. PE_PGRS30 co-localized with PHB2, not in mitochondria, but in lysosomes. The maintenance of mitochondrial structure by PHB2 was impaired in response to the PGRS domain. These results indicated that PE_PGRS30 reduces PHB2 in mitochondria, resulting in mitochondrial dysfunction and cellular apoptosis.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1080369/fullPE_PGRS30PHB2tuberculosismacrophagesapoptosismitochondria |
| spellingShingle | Kazunori Matsumura Satoshi Takaki Teruo Kirikae Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference Frontiers in Microbiology PE_PGRS30 PHB2 tuberculosis macrophages apoptosis mitochondria |
| title | Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference |
| title_full | Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference |
| title_fullStr | Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference |
| title_full_unstemmed | Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference |
| title_short | Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference |
| title_sort | mycobacterial protein pe pgrs30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference |
| topic | PE_PGRS30 PHB2 tuberculosis macrophages apoptosis mitochondria |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1080369/full |
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