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Mitofusin 2-Deficiency Suppresses Mycobacterium tuberculosis Survival in Macrophages

by Junghwan Lee 1,2, Ji-Ae Choi 1,2,3, Soo-Na Cho 1,2, Sang-Hun Son 1,2 and Chang-Hwa Song 1,2,3,*
1
Department of Medical Science, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
2
Department of Microbiology, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
3
Research Institute for Medical Sciences, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
*
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1355; https://doi.org/10.3390/cells8111355
Received: 8 August 2019 / Revised: 15 October 2019 / Accepted: 29 October 2019 / Published: 30 October 2019
Apoptosis is an important host defense mechanism against mycobacterial infection. However, the molecular mechanisms regulating apoptosis during mycobacterial infection are not well known. Recent reports suggest that bacterial infection regulates mitochondrial fusion and fission in various ways. Here, we investigated the role of mitochondria in Mycobacterium tuberculosis (Mtb)-infected macrophages. Mtb H37Rv (Rv) infection induced mitofusin 2 (MFN2) degradation, leading to mitochondrial fission. Interestingly, Mtb H37Ra (Ra) infection induced significantly greater mitochondrial fragmentation than Rv infection. Mtb-mediated Parkin, an E3 ubiquitin ligase, contributed to the degradation of MFN2. To evaluate the role of endoplasmic reticulum stress in the production of Parkin during Mtb infection, we analyzed Parkin production in 4-phenylbutyric acid (4-PBA)-pretreated macrophages. Pretreatment with 4-PBA reduced Parkin production in Mtb-infected macrophages. In contrast, the level of MFN2 production recovered to a level similar to that of the unstimulated control. In addition, Ra-infected macrophages had reduced mitochondrial membrane potential (MMP) compared to those infected with Rv. Interestingly, intracellular survival of mycobacteria was decreased in siMFN2-transfected macrophages; in contrast, overexpression of MFN2 in macrophages increased Mtb growth compared with the control. View Full-Text
Keywords: MFN2; mitochondria; apoptosis; Mycobacterium; ER stress MFN2; mitochondria; apoptosis; Mycobacterium; ER stress
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Lee, J.; Choi, J.-A.; Cho, S.-N.; Son, S.-H.; Song, C.-H. Mitofusin 2-Deficiency Suppresses Mycobacterium tuberculosis Survival in Macrophages. Cells 2019, 8, 1355.

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