Role of mitochondrial autophagy mediated by PINK1/Parkin signaling pathway in severe pneumonia_West China Medical Journal

Authors：

SHI Rui ¹ ,  SHAO Yaxin ² , TIAN Xiaoyu ³ , CAI Lingling ⁴

1. Department of Pediatrics, Huairou Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing 101400, P. R. China;
2. Department of Pediatrics, Pinggu Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing 101299, P. R. China;
3. Department of Emergency Medicine, Huairou Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing 101400, P. R. China;
4. Department of Dermatology, Dongfang Hospital of Beijing University of Chinese Medicine (Second Clinical Medical College of Beijing University of Chinese Medicine), Beijing 100078, P. R. China;

Corresponding author：

SHAO Yaxin, Email: cux7343@163.com

Keywords：

Severe pneumonia; mitochondrial autophagy; homologous phosphatase tensin induced kinase 1; Parkinson’s protein; signaling pathway

DOI：

10.7507/1002-0179.202308104

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the role of mitochondrial autophagy mediated by PINK1 (homologous phosphatase tensin induced kinase 1) /Parkin (Parkinson’s protein) signaling pathway in severe pneumonia of rats. Methods Twenty rats were randomly divided into control group and model group (severe pneumonia model), with 10 rats in each group, to explore the effects of severe pneumonia on lung function and pathology in rats. Then, 30 rats were randomly divided into control group, model group and mdivi-1 (mitochondrial autophagy inhibitor) group, with 10 rats in each group, to further explore the effects of severe pneumonia on mitochondrial autophagy indicators of rats. Results Compared with the control group, the resting ventilation volume [(3.44±0.22) vs. (1.58±0.18) mL/min] and airway resistance ratio (77.48±3.84 vs. 47.76±5.54) in the model group were decreased (P<0.05). In the model group, the lung tissue was injured and a large number of inflammatory cells were infiltrated. The protein and mRNA expression levels of Parkin, PINK1 and microtubule-associated protein1 light chain 3 in lung tissues of model group were increased (P<0.05). Compared with model group, the ratio of resting ventilator-to-airway resistance in mdivi-1 group increased (P<0.05). The injury and inflammatory infiltration of lung tissue were improved in mdivi-1 group. The expression levels of Parkin, PINK1 and microtubule-associated protein1 light chain 3 protein and mRNA in lung tissues of mdivi-1 group were decreased (P<0.05). Conclusion Mdivi-1 can improve the abnormal lung function structure in rats with severe pneumonia, and the mechanism may be related to mitochondrial autophagy mediated by PINK1/Parkin signaling pathway.

Citation： SHI Rui, SHAO Yaxin, TIAN Xiaoyu, CAI Lingling. Role of mitochondrial autophagy mediated by PINK1/Parkin signaling pathway in severe pneumonia. West China Medical Journal, 2024, 39(4): 567-572. doi: 10.7507/1002-0179.202308104 Copy

1.	Nair GB, Niederman MS. Updates on community acquired pneumonia management in the ICU. Pharmacol Ther, 2021, 217: 107663.
2.	Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases. EMBO J, 2021, 40(19): e108863.
3.	王健龄. PINK1/Parkin介导的线粒体自噬在无机砷调节肺脏巨噬细胞极化中的作用研究. 唐山: 华北理工大学, 2022.
4.	Imberechts D, Kinnart I, Wauters F, et al. DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain, 2022, 145(12): 4368-4384.
5.	Mora AL, Bueno M, Rojas M. Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis. J Clin Invest, 2017, 127(2): 405-414.
6.	Ito A, Hashimoto M, Tanihata J, et al. Involvement of Parkin-mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease-related sarcopenia. J Cachexia Sarcopenia Muscle, 2022, 13(3): 1864-1882.
7.	陈兴, 李红卫, 赵永健, 等. Pink1/Parkin介导的线粒体自噬在急性肺损伤中的作用研究进展. 吉林医学, 2022, 43(12): 3334-3337.
8.	刘燕, 赵星, 刘邦祺. 重庆市沙坪坝区重症肺炎患者流行病学调查. 公共卫生与预防医学, 2021, 32(4): 146-149.
9.	罗成, 叶远航, 盛国光, 等. 中医药治疗重症肺炎的研究进展. 中国中医急症, 2023, 32(5): 929-932.
10.	裴飞, 吴健锋. 重症肺炎与炎症风暴: 共识与争议. 中国实用内科杂志, 2022, 42(3): 182-185.
11.	郭枫, 乐道平, 陈晶, 等. 乌司他丁联合美罗培南对老年重症肺炎患者炎症介质和氧化应激的影响. 中国老年学杂志, 2022, 42(9): 2134-2136.
12.	胡婧, 周玉玲, 刘坤. 橙皮苷对重症肺炎大鼠肺组织炎症和细胞凋亡影响. 中国免疫学杂志, 2023, 39(4): 727-732, 738.
13.	Zhuang N, Li L, Chen S, et al. PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control. Cell Death Dis, 2016, 7(12): e2501.
14.	Wang N, Zhu P, Huang R, et al. PINK1: the guard of mitochondria. Life Sci, 2020, 259: 118247.
15.	Miao CC, Hwang W, Chu LY, et al. LC3A-mediated autophagy regulates lung cancer cell plasticity. Autophagy, 2022, 18(4): 921-934.

1. Nair GB, Niederman MS. Updates on community acquired pneumonia management in the ICU. Pharmacol Ther, 2021, 217: 107663.
2. Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases. EMBO J, 2021, 40(19): e108863.
3. 王健龄. PINK1/Parkin介导的线粒体自噬在无机砷调节肺脏巨噬细胞极化中的作用研究. 唐山: 华北理工大学, 2022.
4. Imberechts D, Kinnart I, Wauters F, et al. DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain, 2022, 145(12): 4368-4384.
5. Mora AL, Bueno M, Rojas M. Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis. J Clin Invest, 2017, 127(2): 405-414.
6. Ito A, Hashimoto M, Tanihata J, et al. Involvement of Parkin-mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease-related sarcopenia. J Cachexia Sarcopenia Muscle, 2022, 13(3): 1864-1882.
7. 陈兴, 李红卫, 赵永健, 等. Pink1/Parkin介导的线粒体自噬在急性肺损伤中的作用研究进展. 吉林医学, 2022, 43(12): 3334-3337.
8. 刘燕, 赵星, 刘邦祺. 重庆市沙坪坝区重症肺炎患者流行病学调查. 公共卫生与预防医学, 2021, 32(4): 146-149.
9. 罗成, 叶远航, 盛国光, 等. 中医药治疗重症肺炎的研究进展. 中国中医急症, 2023, 32(5): 929-932.
10. 裴飞, 吴健锋. 重症肺炎与炎症风暴: 共识与争议. 中国实用内科杂志, 2022, 42(3): 182-185.
11. 郭枫, 乐道平, 陈晶, 等. 乌司他丁联合美罗培南对老年重症肺炎患者炎症介质和氧化应激的影响. 中国老年学杂志, 2022, 42(9): 2134-2136.
12. 胡婧, 周玉玲, 刘坤. 橙皮苷对重症肺炎大鼠肺组织炎症和细胞凋亡影响. 中国免疫学杂志, 2023, 39(4): 727-732, 738.
13. Zhuang N, Li L, Chen S, et al. PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control. Cell Death Dis, 2016, 7(12): e2501.
14. Wang N, Zhu P, Huang R, et al. PINK1: the guard of mitochondria. Life Sci, 2020, 259: 118247.
15. Miao CC, Hwang W, Chu LY, et al. LC3A-mediated autophagy regulates lung cancer cell plasticity. Autophagy, 2022, 18(4): 921-934.

West China Medical Journal

Role of mitochondrial autophagy mediated by PINK1/Parkin signaling pathway in severe pneumonia

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content