Bcl-2 Proteins Regulate Mitophagy in Lipopolysaccharide-Induced Acute Lung Injury via PINK1/Parkin Signaling Pathway

被引：119

作者：

Zhang, Zhihao ^{[1
]}

Chen, Zhugui ^{[2
]}

Liu, Ruimeng ^{[1
]}

Liang, Qingchun ^{[3
]}

Peng, Zhiyong ^{[1
]}

Yin, Shuang ^{[1
]}

Tang, Jing ^{[2
]}

Gong, Ting ^{[1
]}

Liu, Youtan ^{[1
]}

机构：

[1] Southern Med Univ, Shenzhen Hosp, Dept Anesthesiol, 1333 Xinhu Rd, Shenzhen 518110, Guangdong, Peoples R China

[2] Guangdong Med Univ, Affiliated Hosp, Dept Anesthesiol, Renmindadao Rd, Zhanjiang 524002, Guangdong, Peoples R China

[3] Southern Med Univ, Affiliated Hosp 3, Dept Anesthesiol, Guangzhou 510000, Peoples R China

来源：

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | 2020年 / 2020卷

基金：

中国国家自然科学基金;

关键词：

MITOCHONDRIAL QUALITY-CONTROL; PARKIN; AUTOPHAGY; DEGRADATION; MECHANISMS; PROTEASOME; APOPTOSIS; DISEASE; SEPSIS; FAMILY;

D O I：

10.1155/2020/6579696

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Mitophagy is involved in sepsis-induced acute lung injury (ALI). Bcl-2 family proteins play an important role in mitochondrial homeostasis. However, whether targeting Bcl-2 proteins (Bcl-2 and Bad) could influence mitophagy in ALI remains unclear. In this study, lipopolysaccharide (LPS) was used to induce injury in A549 cells and ALI in mice. LPS treatment resulted in elevated cell apoptosis, enhanced mitophagy, decreased Bcl-2 expression, increased Bad expression, and activation of PINK1/Parkin signaling in cells and lung tissues. Both Bcl-2 overexpression and Bad knockdown attenuated LPS-induced injury, inhibited cell apoptosis and mitophagy, and improved survival. Atg5 knockout (KO) inhibited LPS-induced cell apoptosis. Furthermore, Bcl-2 proteins regulated mitophagy by modulating the recruitment of Parkin from the cytoplasm to mitochondria via direct protein-protein interactions. These results were further confirmed in Park2 KO cells and Park2(-/-) mice. This is the first study to demonstrate that Bcl-2 proteins regulated mitophagy in LPS-induced ALI via modulating the PINK1/Parkin signaling pathway, promoting new insights into the mechanisms and investigation of therapeutic strategies for a septic patient with ALI.

引用

页数：20

共 52 条

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