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分枝杆菌蛋白PE_PGRS30通过干扰抑癌蛋白2的线粒体功能诱导巨噬细胞凋亡。

Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference.

作者信息

Matsumura Kazunori, Takaki Satoshi, Kirikae Teruo

机构信息

Department of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.

Graduate School of Medicine, Juntendo University, Tokyo, Japan.

出版信息

Front Microbiol. 2023 Jan 27;14:1080369. doi: 10.3389/fmicb.2023.1080369. eCollection 2023.


DOI:10.3389/fmicb.2023.1080369
PMID:36778852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9911437/
Abstract

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 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 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.

摘要

PE_PGRS30属于PE_PGRS蛋白家族,其特征在于保守的脯氨酸-谷氨酸(PE)结构域和典型的富含GC的多态性序列(PGRS)结构域。PE_PGRS30是一种诱导巨噬细胞死亡的毒力因子。我们发现RAW264.7细胞和小鼠肺泡巨噬细胞对PE_PGRS30产生凋亡反应。宿主蛋白抑制素2(PHB2)被鉴定为靶分子。PE_PGRS30和PHB2分别通过PGRS结构域和线粒体靶向序列相互作用。PHB2过表达减少了巨噬细胞对PE_PGRS30的凋亡反应。PE_PGRS30与PHB2共定位,不在线粒体中,而是在溶酶体中。响应PGRS结构域,PHB2对线粒体结构的维持受到损害。这些结果表明,PE_PGRS30减少了线粒体中的PHB2,导致线粒体功能障碍和细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/fdca1eb3550f/fmicb-14-1080369-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/76bfb3387612/fmicb-14-1080369-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/6443e21b07b0/fmicb-14-1080369-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/a03482fb0751/fmicb-14-1080369-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/87f1b8b270db/fmicb-14-1080369-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/3696e0b9edd9/fmicb-14-1080369-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/fdca1eb3550f/fmicb-14-1080369-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/76bfb3387612/fmicb-14-1080369-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/6443e21b07b0/fmicb-14-1080369-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/a03482fb0751/fmicb-14-1080369-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/87f1b8b270db/fmicb-14-1080369-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/3696e0b9edd9/fmicb-14-1080369-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5874/9911437/fdca1eb3550f/fmicb-14-1080369-g006.jpg

相似文献

[1]
Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference.

Front Microbiol. 2023-1-27

[2]
Impact of protein domains on PE_PGRS30 polar localization in Mycobacteria.

PLoS One. 2014-11-12

[3]
PE_PGRS30 is required for the full virulence of Mycobacterium tuberculosis.

Cell Microbiol. 2011-12-13

[4]
The PGRS domain is responsible for translocation of PE_PGRS30 to cell poles while the PE and the C-terminal domains localize it to the cell wall.

FEBS Lett. 2014-2-11

[5]
PE_PGRS30 of Mycobacterium tuberculosis mediates suppression of proinflammatory immune response in macrophages through its PGRS and PE domains.

Microbes Infect. 2016-9

[6]
The Rv1651c-encoded PE-PGRS30 protein expressed in Mycobacterium smegmatis exhibits polar localization and modulates its growth profile.

FEMS Microbiol Lett. 2011-7-25

[7]
PE_PGRS: Vital proteins in promoting mycobacterial survival and modulating host immunity and metabolism.

Cell Microbiol. 2021-3

[8]
The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4.

mBio. 2018-6-19

[9]
PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis.

Autophagy. 2019-6-16

[10]
Execution of macrophage apoptosis by PE_PGRS33 of Mycobacterium tuberculosis is mediated by Toll-like receptor 2-dependent release of tumor necrosis factor-alpha.

J Biol Chem. 2007-1-12

引用本文的文献

[1]
Evolution of the PE_PGRS Proteins of Mycobacteria: Are All Equal or Are Some More Equal than Others?

Biology (Basel). 2025-2-28

[2]
Prohibitins in infection: potential therapeutic targets.

Future Microbiol. 2025-3

[3]
Epigenetic Mechanisms Induced by to Promote Its Survival in the Host.

Int J Mol Sci. 2024-11-2

[4]
PE_PGRS38 Enhances Intracellular Survival of Mycobacteria by Inhibiting TLR4/NF-κB-Dependent Inflammation and Apoptosis of the Host.

Biology (Basel). 2024-4-30

[5]
Temporal Profiling of Host Proteome against Different Strains Reveals Delayed Epigenetic Orchestration.

Microorganisms. 2023-12-16

本文引用的文献

[1]
PGRS domain structures: Doomed to sail the mycomembrane.

PLoS Pathog. 2022-9

[2]
Mycobacterium tuberculosis PE17 (Rv1646) promotes host cell apoptosis via host chromatin remodeling mediated by reduced H3K9me3 occupancy.

Microb Pathog. 2021-10

[3]
Protein PE6 (Rv0335c), a Novel TLR4 Agonist, Evokes an Inflammatory Response and Modulates the Cell Death Pathways in Macrophages to Enhance Intracellular Survival.

Front Immunol. 2021-7-12

[4]
Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis.

FASEB J. 2021-6

[5]
Recombinant Rv1654 protein of Mycobacterium tuberculosis induces mitochondria-mediated apoptosis in macrophage.

Microbiol Immunol. 2021-4

[6]
Isolation and Long-term Cultivation of Mouse Alveolar Macrophages.

Bio Protoc. 2019-7-20

[7]
PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis.

Autophagy. 2019-6-16

[8]
Bif-1 Interacts with Prohibitin-2 to Regulate Mitochondrial Inner Membrane during Cell Stress and Apoptosis.

J Am Soc Nephrol. 2019-5-24

[9]
PE_PGRS62 promotes the survival of Mycobacterium smegmatis within macrophages via disrupting ER stress-mediated apoptosis.

J Cell Physiol. 2019-4-1

[10]
Cell death at the cross roads of host-pathogen interaction in Mycobacterium tuberculosis infection.

Tuberculosis (Edinb). 2018-12

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