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线粒体自噬受损会在感染结核分枝杆菌的巨噬细胞中引发抗菌反应。

Impaired mitophagy induces antimicrobial responses in macrophages infected with Mycobacterium tuberculosis.

作者信息

Lee Junghwan, Lee Seong-Ahn, Son Sang-Hun, Choi Ji-Ae, Nguyen Tam Doan, Kim Jaewhan, Son Doyi, Song Chang-Hwa

机构信息

Department of Microbiology, Department of Medical Science, College of Medicine, Chungnam National University, 266 Munhwa‑ro, Jung‑gu, Daejeon, 35015, South Korea.

Department of Medical Science, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea.

出版信息

Cell Biosci. 2023 Aug 30;13(1):158. doi: 10.1186/s13578-023-01107-2.

DOI:10.1186/s13578-023-01107-2
PMID:37649112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10470153/
Abstract

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.

摘要

背景

线粒体自噬，即线粒体选择性自噬，在细胞应对应激时维持细胞内稳态中起关键作用。然而，线粒体自噬在感染过程中巨噬细胞内的作用尚未阐明。为了确定线粒体自噬是否调节细胞内病原体的存活，用细胞内细菌结核分枝杆菌（Mtb）感染巨噬细胞。

结果

我们发现，感染Mtb的巨噬细胞通过激活BCL2/腺病毒E1B 19 kDa蛋白相互作用蛋白3（BNIP3）诱导线粒体自噬。相反，缺乏BNIP3的巨噬细胞无法诱导线粒体自噬，导致在应对Mtb感染时线粒体膜电位降低。此外，与对照相比，由于BNIP3缺乏导致的受损线粒体积累产生了更高水平的线粒体活性氧（mROS），抑制了Mtb的细胞内存活。我们观察到，siBNIP3抑制了小鼠肺内细胞内的Mtb。

结论

我们发现BNIP3在Mtb感染期间线粒体自噬的调节中起关键作用。线粒体自噬的抑制通过增加mROS的产生来抑制巨噬细胞中Mtb的生长。因此，BNIP3可能是结核病治疗的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42af/10470153/20f8502c7c8b/13578_2023_1107_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42af/10470153/6aea37a8e1c7/13578_2023_1107_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42af/10470153/530e756ee5c5/13578_2023_1107_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42af/10470153/6ca0c53b9c25/13578_2023_1107_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42af/10470153/20f8502c7c8b/13578_2023_1107_Fig10_HTML.jpg

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