Autophagy Promoted by Pakinson’s Disease Related Protein Pink1
Abstract
To investigate the function of Parkinson's disease(PD)-related protein Pink1 in autophagy. Methods Pink1, autophagy inhibitor Bcl-XL and autophagy induced-factor Beclin1 were amplified with RT-PCR and contructed into pcDNA3.1(+)vector. The stable HEK293 cell line of Pink1 expression was established through the lentivirus system. Pink1, Bcl-XL and Beclin1 were tansfected into the HEK293 Cell Line. Co-Immunoprecipitation and Western blot were performed to determine the interaction between Pink1 and Bcl-XL, the effect of Pink1 on the interaction between Bcl-XL and Beclin1,and the function of Pink1 in autophagy. Results There was a new interaction between Pink1 and antophagy inhibitor Bcl-XL. Overexpressed Pink1 promoted the dissociation of autophagy induced-factor Beclin1 from Bcl-XL. Overexpressed Pink1 increased the autophagic protein LC3Ⅱ/LC3Ⅰ. Conclusion Pakinson's disease related protein Pink1 promotes the dissociation of autophagy induced-factor Beclin1 from antophagy inhibitor Bcl-XL and promotes autophagy.
Keywords: Pink1, Bcl-XL, Beclin1, Mitochondria, Autophagy, Parkinson's disease
Full Text:
PDFReferences
Abeliovich A. Flint Beal M. Parkinsonsim genes: culprits and clues. J Neurochem,2006;99(9): 1062-1072.
Abou-Sleiman PM. Muqit MM. Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat Rev Neurosci*2006;7(9) :207-219.
Clark IE, Dodson MW. Jiang C, et al. Drosophila pinkl is required for mitochondrial function and interacts genetically with parkin. Nature,2006$441 (3); 1162-1166.
Yang Y, Gehrke S, Imai Y, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pinkl is rescued by Parkin. PNAS, 2006;103(1):10793-10798.
Plum-Favreau H, Klupsch K. Moisoi N, et al. The mitochondrial protease HtrA2 is regulated by Parkinson 9 s disease-associated kinase Pinkl. Nat Cell Biol. 2007; 9 ( 3 ) ; 1243-1252.
Jeehye P. Sung Bae L, Sungkyu L, et al. Mitochondrial dysfunction in Drosophila Pinkl mutants is complemented by parkin. Nature,2006; 441 (4) ; 1157-1161.
Hui X, Danling W. Linan C, et al. Parkin, Pinkl, and DJ-1 form an ubiquitin E3 ligase complex promoting unfolded protein degradation. J Clin Invest,2009; 119(3) : 650-660.
Cristofol Vives-B, Chun Z, Yong H, et al. PINK 1-dependent recruitment of Parkin to mitochondria in mitophagy. PNAS, 2010;107(1):378-383.
Nickie CC, Anna MS, Anh HP. et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet,2011 ;20(9): 1726-1737.
Sven G. Kria MH, Diana S, et al. Pinkl/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTMl. Nat Cell Biol,2010; 12(2):445-452.
Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys,2007;462(9):245-253.
Komatsu M, Ueno T, Waguri S, et al. Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons. Cell Death Differ,2007; 14(1);887-894.
Martinez-Vicente M, Cuervo AM. Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol,2007;6( 1):352-361.
Winslow AR, Rubinsztein DC. Autophagy in neurodegeneration and development. Biochim Biophys Acta, 2008;1782(2):723-729.
Michiorri S, Belmetti V, Giarda E, et al. The Parkinson- associated protein Pinkl interacts with Beclinl and promotes autophagy. Cell Death Differ,2010; 1 (3); 1-13.
Chun Z, Yong H. Yufang S, el al. The kinase domain of mitochondrial PINK1 faces the cytoplasm. PNAS, 2008; 105 (3):12022-12027.
Ruben KI), Salvatore J, Cherra H, et al. Loss of PINK1 function promotes Mitophagy through effects on Oxidative Stress and Mitochondrial Fission. JBC. 2009; 284 ( 2): 13843- 13855.
Einat Z, Hanna B. Liat M. et al. DAP-kinase-mediated Phosphorylation on the BH3 domain of beclinl promotes dissociation of beclinl from Bcl-XL and induction of autophagy. EMBO Reports,2009; 10( 1);285-292.
Refbacks
- There are currently no refbacks.



