Arabidopsis AtPARK13, which confers thermotolerance, targets misfolded proteins.
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.
From the Department of Biological Sciences, St. John's University, New York, New York 11439.
Indranil
I
Basak
From the Department of Biological Sciences, St. John's University, New York, New York 11439.
Ramavati
R
Pal
From the Department of Biological Sciences, St. John's University, New York, New York 11439.
Ketan S
KS
Patil
From the Department of Biological Sciences, St. John's University, New York, New York 11439.
Aisling
A
Dunne
the Department of Chemistry, York College of the City University of New York, New York, New York 11451.
Hsin-Pin
HP
Ho
From the Department of Biological Sciences, St. John's University, New York, New York 11439.
Sungsu
S
Lee
the Department of Molecular and Applied Biosciences, University of Westminster, London W1W 6UW, United Kingdom, and.
Diluka
D
Peiris
the Norwegian Center for Movement Disorders, Stavanger University Hospital, 4068 Stavanger, Norway.
Jodi
J
Maple-Grødem
the Department of Molecular and Applied Biosciences, University of Westminster, London W1W 6UW, United Kingdom, and.
Mark
M
Odell
the Department of Chemistry, York College of the City University of New York, New York, New York 11451.
Emmanuel J
EJ
Chang
the Norwegian Center for Movement Disorders, Stavanger University Hospital, 4068 Stavanger, Norway.
Jan Petter
JP
Larsen
From the Department of Biological Sciences, St. John's University, New York, New York 11439, the Norwegian Center for Movement Disorders, Stavanger University Hospital, 4068 Stavanger, Norway mollers@stjohns.edu.
Simon G
SG
Møller
D000222:Adaptation, Physiological / Q000235:genetics*; D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D006358:Hot Temperature; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D030821:Plants, Genetically Modified; D000071617:Protein Deglycase DJ-1; D058767:Protein Unfolding; D059748:Proteolysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
D029681:Arabidopsis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D024101:Mitochondrial Proteins; D015513:Oncogene Proteins; D051844:alpha-Synuclein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C000592578:PARK13 protein, Arabidopsis; D010447:Peptide Hydrolases; D057057:Serine Proteases
Arabidopsis; Heat Stress; Parkinson Disease; Protease; Proteomics; Stress