Preconditioning Involves Selective Mitophagy Mediated by Parkin and p62/SQSTM1

作者: Chengqun Huang , Allen M. Andres , Eric P. Ratliff , Genaro Hernandez , Pamela Lee

DOI: 10.1371/JOURNAL.PONE.0020975

关键词:

摘要: Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining homeostasis. However, the mechanisms that govern selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown be essential clearance mitochondria. Parkin expressed heart, yet its function not investigated context cardioprotection. We previously reported autophagy required cardioprotection by ischemic preconditioning (IPC). In present study, we used simulated ischemia (sI) vitro and IPC hearts investigate role mediating ex vivo vivo. HL-1 cells, sI induced translocation elimination. Langendorff-perfused rat mice subjected regional IPC. Mitochondrial depolarization with uncoupling agent similarly cells hearts. loss was blunted Atg5-deficient revealing requirement Consistent previous reports indicating a p62/SQSTM1 mitophagy, found depletion p62 attenuated mitophagy exacerbated cell death cardiomyocytes sI. While wild type showed increase ubiquitination, knockout exhibited IPC-induced Importantly, ablation abolished cardioprotective effects These results reveal first time crucial

参考文章(43)
R. S. Decker, K. Wildenthal, Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes. American Journal of Pathology. ,vol. 98, pp. 425- 444 ,(1980)
N. Shimizu, S. Asakawa, S. Minoshima, T. Kitada, N. Hattori, H. Matsumine, M. Yokochi, Y. Yamamura, Y. Mizuno, PARKIN as a pathogenic gene for autosomal recessive juvenile parkinsonism. Journal of Neural Transmission-supplement. pp. 19- 30 ,(2000) , 10.1007/978-3-7091-6284-2_2
Tohru Kitada, Shuichi Asakawa, Nobutaka Hattori, Hiroto Matsumine, Yasuhiro Yamamura, Shinsei Minoshima, Masayuki Yokochi, Yoshikuni Mizuno, Nobuyoshi Shimizu, Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism Nature. ,vol. 392, pp. 605- 608 ,(1998) , 10.1038/33416
Kei Okatsu, Keiko Saisho, Midori Shimanuki, Kazuto Nakada, Hiroshi Shitara, Yu-shin Sou, Mayumi Kimura, Shigeto Sato, Nobutaka Hattori, Masaaki Komatsu, Keiji Tanaka, Noriyuki Matsuda, p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria Genes to Cells. ,vol. 15, pp. no- no ,(2010) , 10.1111/J.1365-2443.2010.01426.X
E. Ziviani, R. N. Tao, A. J. Whitworth, Drosophila Parkin requires PINK1 for mitochondrial translocation and ubiquitinates Mitofusin Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 5018- 5023 ,(2010) , 10.1073/PNAS.0913485107
Mark W Dodson, Ming Guo, Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease Current Opinion in Neurobiology. ,vol. 17, pp. 331- 337 ,(2007) , 10.1016/J.CONB.2007.04.010
Akiko Kuma, Masahiko Hatano, Makoto Matsui, Akitsugu Yamamoto, Haruaki Nakaya, Tamotsu Yoshimori, Yoshinori Ohsumi, Takeshi Tokuhisa, Noboru Mizushima, The role of autophagy during the early neonatal starvation period Nature. ,vol. 432, pp. 1032- 1036 ,(2004) , 10.1038/NATURE03029
Noboru Mizushima, Beth Levine, Ana Maria Cuervo, Daniel J. Klionsky, Autophagy fights disease through cellular self-digestion Nature. ,vol. 451, pp. 1069- 1075 ,(2008) , 10.1038/NATURE06639
Wen-Xing Ding, Hong-Min Ni, Min Li, Yong Liao, Xiaoyun Chen, Donna B. Stolz, Gerald W. Dorn, Xiao-Ming Yin, Nix Is Critical to Two Distinct Phases of Mitophagy, Reactive Oxygen Species-mediated Autophagy Induction and Parkin-Ubiquitin-p62-mediated Mitochondrial Priming Journal of Biological Chemistry. ,vol. 285, pp. 27879- 27890 ,(2010) , 10.1074/JBC.M110.119537