Arabidopsis AtPARK13, which confers thermotolerance, targets misfolded proteins

Basak, Indranil, Pal, Ramavati, Patil, Ketan S. , Dunne, Aisling, Ho, Hsin-Pin, Lee, Sungsu, Peiris, Diluka, Maple-Grødem, Jodi, Odell, Mark, Chang, Emmanuel J., Larsen, Jan Petter and Møller, Simon G. (2014) Arabidopsis AtPARK13, which confers thermotolerance, targets misfolded proteins. Journal of Biological Chemistry, 289 (21). pp. 14458-14469. ISSN 0021-9258

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Mutations in HTRA2/Omi/PARK13 have been implicated in Parkinson disease (PD). PARK13 is a neuroprotective serine protease; however, little is known about how PARK13 confers stress protection and which protein targets are directly affected by PARK13. We have reported that Arabidopsis thaliana represents a complementary PD model, and here we demonstrate that AtPARK13, similar to human PARK13 (hPARK13), is a mitochondrial protease. We show that the expression/accumulation of AtPARK13 transcripts are induced by heat stress but not by other stress conditions, including oxidative stress and metals. Our data show that elevated levels of AtPARK13 confer thermotolerance in A. thaliana. Increased temperatures accelerate protein unfolding, and we demonstrate that although AtPARK13 can act on native protein substrates, unfolded proteins represent better AtPARK13 substrates. The results further show that AtPARK13 and hPARK13 can degrade the PD proteins α-synuclein (SNCA) and DJ-1/PARK7 directly, without autophagy involvement, and that misfolded SNCA and DJ-1 represent better substrates than their native counterparts. Comparative proteomic profiling revealed AtPARK13-mediated proteome changes, and we identified four proteins that show altered abundance in response to AtPARK13 overexpression and elevated temperatures. Our study not only suggests that AtPARK13 confers thermotolerance by degrading misfolded protein targets, but it also provides new insight into possible roles of this protease in neurodegeneration.

Keywords:Parkinson Disease, Arabidopsis, Protease, Proteomics, Stress, Heat Stress
Subjects:C Biological Sciences > C720 Biological Chemistry
B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Life Sciences
ID Code:38022
Deposited On:28 Nov 2019 09:34

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