Page 26 - M. Immunology

[M. Immunology-19]

Role of mitochondria in Mycobacterium tuberculosis infected

macrophages

Junghwan Lee¹˙², Ji-Ae Choi¹˙², Soo-Na Cho¹˙², Sang-Hun Son¹˙², Doan Tam Nguyen¹˙², Seong Ahn Lee¹˙²,
Chang-Hwa Song¹˙²˙*

¹Department of Medical Science, Chungnam National University, Daejeon 35015, South Korea, ²Department of

Microbiology, Chungnam National University, Daejeon 35015, South Korea

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. Mtb H37Ra (Ra) infection induced significantly
greater mitochondrial fragmentation than Rv infection. Mtb-mediated Parkin 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.