Impaired mitophagy induces antimicrobial responses in macrophages infected with Mycobacterium tuberculosis
© 2023. Society of Chinese Bioscientists in America (SCBA)..
BACKGROUND: Mitophagy, mitochondrial selective autophagy, plays a pivotal role in the maintenance of cellular homeostasis in response to cellular stress. However, the role of mitophagy in macrophages during infection has not been elucidated. To determine whether mitophagy regulates intracellular pathogen survival, macrophages were infected with Mycobacterium tuberculosis (Mtb), an intracellular bacterium.
RESULTS: We showed that Mtb-infected macrophages induced mitophagy through BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) activation. In contrast, BNIP3-deficient macrophages failed to induce mitophagy, resulting in reduced mitochondrial membrane potential in response to Mtb infection. Moreover, the accumulation of damaged mitochondria due to BNIP3 deficiency generated higher levels of mitochondrial reactive oxygen species (mROS) compared to the control, suppressing the intracellular survival of Mtb. We observed that siBNIP3 suppressed intracellular Mtb in mice lungs.
CONCLUSION: We found that BNIP3 plays a critical role in the regulation of mitophagy during Mtb infection. The inhibition of mitophagy suppresses Mtb growth in macrophages through increased mROS production. Therefore, BNIP3 might be a novel therapeutic target for tuberculosis treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Cell & bioscience - 13(2023), 1 vom: 30. Aug., Seite 158 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Junghwan [VerfasserIn] |
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| Links: |
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| Themen: |
BNIP3 |
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| Anmerkungen: |
Date Revised 20.11.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s13578-023-01107-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361469713 |
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| 245 | 1 | 0 | |a Impaired mitophagy induces antimicrobial responses in macrophages infected with Mycobacterium tuberculosis |
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| 500 | |a Date Revised 20.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023. Society of Chinese Bioscientists in America (SCBA). | ||
| 520 | |a BACKGROUND: Mitophagy, mitochondrial selective autophagy, plays a pivotal role in the maintenance of cellular homeostasis in response to cellular stress. However, the role of mitophagy in macrophages during infection has not been elucidated. To determine whether mitophagy regulates intracellular pathogen survival, macrophages were infected with Mycobacterium tuberculosis (Mtb), an intracellular bacterium | ||
| 520 | |a RESULTS: We showed that Mtb-infected macrophages induced mitophagy through BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) activation. In contrast, BNIP3-deficient macrophages failed to induce mitophagy, resulting in reduced mitochondrial membrane potential in response to Mtb infection. Moreover, the accumulation of damaged mitochondria due to BNIP3 deficiency generated higher levels of mitochondrial reactive oxygen species (mROS) compared to the control, suppressing the intracellular survival of Mtb. We observed that siBNIP3 suppressed intracellular Mtb in mice lungs | ||
| 520 | |a CONCLUSION: We found that BNIP3 plays a critical role in the regulation of mitophagy during Mtb infection. The inhibition of mitophagy suppresses Mtb growth in macrophages through increased mROS production. Therefore, BNIP3 might be a novel therapeutic target for tuberculosis treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BNIP3 | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Mitophagy | |
| 650 | 4 | |a Mycobacterium tuberculosis | |
| 650 | 4 | |a mROS | |
| 700 | 1 | |a Lee, Seong-Ahn |e verfasserin |4 aut | |
| 700 | 1 | |a Son, Sang-Hun |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Ji-Ae |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Tam Doan |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jaewhan |e verfasserin |4 aut | |
| 700 | 1 | |a Son, Doyi |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Chang-Hwa |e verfasserin |4 aut | |
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