The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
10.1038/ncb1644
Crossref journal-article
Springer Science and Business Media LLC
Nature Cell Biology (297)
Bibliography

Plun-Favreau, H., Klupsch, K., Moisoi, N., Gandhi, S., Kjaer, S., Frith, D., Harvey, K., Deas, E., Harvey, R. J., McDonald, N., Wood, N. W., Martins, L. M., & Downward, J. (2007). The mitochondrial protease HtrA2 is regulated by Parkinson’s disease-associated kinase PINK1. Nature Cell Biology, 9(11), 1243–1252.

Authors 13
  1. Hélène Plun-Favreau (first)
  2. Kristina Klupsch (additional)
  3. Nicoleta Moisoi (additional)
  4. Sonia Gandhi (additional)
  5. Svend Kjaer (additional)
  6. David Frith (additional)
  7. Kirsten Harvey (additional)
  8. Emma Deas (additional)
  9. Robert J. Harvey (additional)
  10. Neil McDonald (additional)
  11. Nicholas W. Wood (additional)
  12. L. Miguel Martins (additional)
  13. Julian Downward (additional)
References 42 Referenced 399
  1. Faccio, L. et al. Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia. J. Biol. Chem. 275, 2581–2588 (2000). (10.1074/jbc.275.4.2581) / J. Biol. Chem. by L Faccio (2000)
  2. Gray, C. W. et al. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur. J. Biochem. 267, 5699–5710 (2000). (10.1046/j.1432-1327.2000.01589.x) / Eur. J. Biochem. by CW Gray (2000)
  3. Hegde, R. et al. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein–caspase interaction. J. Biol. Chem. 277, 432–438 (2002). (10.1074/jbc.M109721200) / J. Biol. Chem. by R Hegde (2002)
  4. Martins, L. M. et al. The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J. Biol. Chem. 277, 439–444 (2002). (10.1074/jbc.M109784200) / J. Biol. Chem. by LM Martins (2002)
  5. Suzuki, Y. et al. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol. Cell 8, 613–621 (2001). (10.1016/S1097-2765(01)00341-0) / Mol. Cell by Y Suzuki (2001)
  6. Verhagen, A. M. et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem. 277, 445–454 (2002). (10.1074/jbc.M109891200) / J. Biol. Chem. by AM Verhagen (2002)
  7. Martins, L. M. et al. Binding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi. J. Biol. Chem. 278, 49417–49427 (2003). (10.1074/jbc.M308659200) / J. Biol. Chem. by LM Martins (2003)
  8. Yang, Q. H., Church-Hajduk, R., Ren, J., Newton, M. L. & Du, C. Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis. Genes Dev. 17, 1487–1496 (2003). (10.1101/gad.1097903) / Genes Dev. by QH Yang (2003)
  9. Jones, J. M. et al. Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature 425, 721–727 (2003). (10.1038/nature02052) / Nature by JM Jones (2003)
  10. Martins, L. M. et al. Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol. Cell. Biol. 24, 9848–9862 (2004). (10.1128/MCB.24.22.9848-9862.2004) / Mol. Cell. Biol. by LM Martins (2004)
  11. Spiess, C., Beil, A. & Ehrmann, M. A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein. Cell 97, 339–347 (1999). (10.1016/S0092-8674(00)80743-6) / Cell by C Spiess (1999)
  12. Walsh, N. P., Alba, B. M., Bose, B., Gross, C. A. & Sauer, R. T. OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain. Cell 113, 61–71 (2003). (10.1016/S0092-8674(03)00203-4) / Cell by NP Walsh (2003)
  13. Strauss, K. M. et al. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum. Mol. Genet. 14, 2099–2111 (2005). (10.1093/hmg/ddi215) / Hum. Mol. Genet. by KM Strauss (2005)
  14. Cilenti, L. et al. Regulation of HAX-1 anti-apoptotic protein by Omi/HtrA2 protease during cell death. J. Biol. Chem. 279, 50295–50301 (2004). (10.1074/jbc.M406006200) / J. Biol. Chem. by L Cilenti (2004)
  15. Valente, E. M. et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158–1160 (2004). (10.1126/science.1096284) / Science by EM Valente (2004)
  16. Bonifati, V. et al. Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes. Neurology 65, 87–95 (2005). (10.1212/01.wnl.0000167546.39375.82) / Neurology by V Bonifati (2005)
  17. Hatano, Y. et al. Novel PINK1 mutations in early-onset parkinsonism. Ann. Neurol. 56, 424–427 (2004). (10.1002/ana.20251) / Ann. Neurol. by Y Hatano (2004)
  18. Li, Y. et al. Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism. Neurology 64, 1955–1957 (2005). (10.1212/01.WNL.0000164009.36740.4E) / Neurology by Y Li (2005)
  19. Rogaeva, E. et al. Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease. Arch. Neurol. 61, 1898–1904 (2004). (10.1001/archneur.61.12.1898) / Arch. Neurol. by E Rogaeva (2004)
  20. Rohe, C. F. et al. Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism. Ann. Neurol. 56, 427–431 (2004). (10.1002/ana.20247) / Ann. Neurol. by CF Rohe (2004)
  21. Obenauer, J. C., Cantley, L. C. & Yaffe, M. B. Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res. 31, 3635–3641 (2003). (10.1093/nar/gkg584) / Nucleic Acids Res. by JC Obenauer (2003)
  22. Kuma, Y. et al. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J. Biol. Chem. 280, 19472–19479 (2005). (10.1074/jbc.M414221200) / J. Biol. Chem. by Y Kuma (2005)
  23. Chandel, N. S. et al. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl Acad. Sci. USA 95, 11715–11720 (1998). (10.1073/pnas.95.20.11715) / Proc. Natl Acad. Sci. USA by NS Chandel (1998)
  24. Li, W. et al. Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. Nature Struct. Biol. 9, 436–441 (2002). (10.1038/nsb795) / Nature Struct. Biol. by W Li (2002)
  25. Wilken, C., Kitzing, K., Kurzbauer, R., Ehrmann, M. & Clausen, T. Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a protease. Cell 117, 483–494 (2004). (10.1016/S0092-8674(04)00454-4) / Cell by C Wilken (2004)
  26. Greenamyre, J. T. & Hastings, T. G. Biomedicine. Parkinson's—divergent causes, convergent mechanisms. Science 304, 1120–1122 (2004). (10.1126/science.1098966) / Science by JT Greenamyre (2004)
  27. Paisan-Ruiz, C. et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595–600 (2004). (10.1016/j.neuron.2004.10.023) / Neuron by C Paisan-Ruiz (2004)
  28. Ramirez, A. et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nature Genet. 38, 1184–1191 (2006). (10.1038/ng1884) / Nature Genet. by A Ramirez (2006)
  29. Zimprich, A. et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601–607 (2004). (10.1016/j.neuron.2004.11.005) / Neuron by A Zimprich (2004)
  30. Beilina, A. et al. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc. Natl Acad. Sci. USA 102, 5703–5708 (2005). (10.1073/pnas.0500617102) / Proc. Natl Acad. Sci. USA by A Beilina (2005)
  31. Silvestri, L. et al. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum. Mol. Genet. 14, 3477–3492 (2005). (10.1093/hmg/ddi377) / Hum. Mol. Genet. by L Silvestri (2005)
  32. Sim, C. H. et al. C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1. Hum. Mol. Genet. 15, 3251–3262 (2006). (10.1093/hmg/ddl398) / Hum. Mol. Genet. by CH Sim (2006)
  33. Harper, S. J. & Wilkie, N. MAPKs: new targets for neurodegeneration. Expert Opin. Ther. Targets 7, 187–200 (2003). (10.1517/14728222.7.2.187) / Expert Opin. Ther. Targets by SJ Harper (2003)
  34. Pridgeon, J. W., Olzmann, J. A., Chin, L. S. & Li, L. PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLOS Biol. 5, e172 (2007). (10.1371/journal.pbio.0050172) / PLOS Biol. by JW Pridgeon (2007)
  35. Young, J. C. & Hartl, F. U. A stress sensor for the bacterial periplasm. Cell 113, 1–2 (2003). (10.1016/S0092-8674(03)00192-2) / Cell by JC Young (2003)
  36. Abou-Sleiman, P. M. et al. A heterozygous effect for PINK1 mutations in Parkinson's disease? Ann. Neurol. 60, 414–419 (2006). (10.1002/ana.20960) / Ann. Neurol. by PM Abou-Sleiman (2006)
  37. Gandhi, S. et al. PINK1 protein in normal human brain and Parkinson's disease. Brain 129, 1720–1731 (2006). (10.1093/brain/awl114) / Brain by S Gandhi (2006)
  38. Vyas, S. et al. Differentiation-dependent sensitivity to apoptogenic factors in PC12 cells. J. Biol. Chem. 279, 30983–30993 (2004). (10.1074/jbc.M400692200) / J. Biol. Chem. by S Vyas (2004)
  39. Evan, G. I., Lewis, G. K., Ramsay, G. & Bishop, J. M. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol. Cell. Biol. 5, 3610–3616 (1985). (10.1128/MCB.5.12.3610) / Mol. Cell. Biol. by GI Evan (1985)
  40. Garner, A. P., Weston, C. R., Todd, D. E., Balmanno, K. & Cook, S. J. ΔMEKK3:ER* activation induces a p38α/β2-dependent cell cycle arrest at the G2 checkpoint. Oncogene 21, 8089–8104 (2002). (10.1038/sj.onc.1206000) / Oncogene by AP Garner (2002)
  41. Rytomaa, M., Lehmann, K. & Downward, J. Matrix detachment induces caspase-dependent cytochrome c release from mitochondria: inhibition by PKB/Akt but not Raf signalling. Oncogene 19, 4461–4468 (2000). (10.1038/sj.onc.1203805) / Oncogene by M Rytomaa (2000)
  42. Abraham, V. C., Taylor, D. L. & Haskins, J. R. High content screening applied to large-scale cell biology. Trends Biotechnol. 22, 15–22 (2004). (10.1016/j.tibtech.2003.10.012) / Trends Biotechnol. by VC Abraham (2004)
Dates
Type When
Created 17 years, 10 months ago (Sept. 30, 2007, 1:09 p.m.)
Deposited 2 years, 3 months ago (May 18, 2023, 3:30 p.m.)
Indexed 1 week ago (Aug. 20, 2025, 8:56 a.m.)
Issued 17 years, 10 months ago (Sept. 30, 2007)
Published 17 years, 10 months ago (Sept. 30, 2007)
Published Online 17 years, 10 months ago (Sept. 30, 2007)
Published Print 17 years, 9 months ago (Nov. 1, 2007)
Funders 0

None

@article{Plun_Favreau_2007, title={The mitochondrial protease HtrA2 is regulated by Parkinson’s disease-associated kinase PINK1}, volume={9}, ISSN={1476-4679}, url={http://dx.doi.org/10.1038/ncb1644}, DOI={10.1038/ncb1644}, number={11}, journal={Nature Cell Biology}, publisher={Springer Science and Business Media LLC}, author={Plun-Favreau, Hélène and Klupsch, Kristina and Moisoi, Nicoleta and Gandhi, Sonia and Kjaer, Svend and Frith, David and Harvey, Kirsten and Deas, Emma and Harvey, Robert J. and McDonald, Neil and Wood, Nicholas W. and Martins, L. Miguel and Downward, Julian}, year={2007}, month=sep, pages={1243–1252} }