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Literature for peptidase S54.009: PARL peptidase

Summary Alignment Tree Sequences Sequence features Distribution Literature Substrates Inhibitors

(Topics flags: M Mutation, I Inhibitor, K Knockout, V Review. To select only the references relevant to a single topic, click the link above. See explanation.)

    2025
  1. An,D., Zhang,C., Zhou,P., Wang,Y., Meng,S., Chen,Y., Xu,W., Xuan,J., Xiong,J., Cheng,J., Gao,R., Wang,J. and Chen,X.
    Cleaving PINK1 or PGAM5? Involvement of PARL in Methamphetamine-Induced Excessive Mitophagy and Neuronal Necroptosis
    CNS Neurosci Ther (2025) 31, e70293-e70293. PubMed  Europe PubMed DOI  PMC  EPMC  K
  2. Brassard,R., Arutyunova,E., Takyi,E., Espinoza-Fonseca,L.M., Young,H., Touret,N. and Lemieux,M.J.
    Transmembrane Parkinson's Disease mutation of PINK1 leads to altered mitochondrial anchoring
    J Biol Chem (2025) , 108253-108253. PubMed  Europe PubMed DOI
  3. d'Angelo,D., Al Saidi,A., Ghirardo,G., Vecellio Reane,D., Gasparini,N., Rizzuto,R. and Raffaello,A.
    Impact of PARL-mediated mitochondrial protease activity on calcium regulation
    Biochim Biophys Acta Mol Cell Res (2025) 1872, 119998-119998. PubMed  Europe PubMed DOI
  4. Ludwig,K. and Heidorn-Czarna,M.
    Mitochondrial Proteases and Their Roles in Mitophagy in Plants, Animals, and Yeast
    Plant Cell Physiol (2025) PubMed  Europe PubMed DOI  V
  5. Sun,N., Barta,H., Chaudhuri,S., Chen,K., Jin,J., Luo,H., Yang,M., Krigman,J., Zhang,R., Sanghvi,S., Sekine,S., Sanders,H., Kolonay,D., Patel,M., Baskin,K., Singh,H., Zhang,P., Xin,G. and Finkel,T.
    Mitophagy mitigates mitochondrial fatty acid beta-oxidation deficient cardiomyopathy
    Nat Commun (2025) 16, 5465-5465. PubMed  Europe PubMed DOI  PMC  EPMC
  6. Wang,S., Wu,X., Bi,W., Xu,J., Hou,L., Li,G., Pan,Y., Zhang,H., Li,M., Du,S., Zhang,M., Liu,D., Jin,S., Shi,X., Tian,Y., Shuai,J., Plikus,M.V., Song,M., Zhou,Z., Yu,L., Lv,C. and Yu,Z.
    ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3
    Nat Commun (2025) 16, 1406-1406. PubMed  Europe PubMed DOI  PMC  EPMC
  7. Yin,S., Zhai,Y., Song,R., Wu,J., Zhang,Y., Yu,M., Ma,H., Shen,M., Lai,X., Jin,W., Xu,Y. and Yan,J.
    PARL stabilizes mitochondrial BCL-2 via Nur77-mediated scaffolding as a therapeutic strategy for Parkinson's disease
    Cell Death Dis (2025) 16, 700-700. PubMed  Europe PubMed DOI  PMC  EPMC  K
  8. Zhou,N., Liu,Z., Shi,Z., Luo,L., Xuan,M., Zhu,R., Hu,K., Zhu,X., Xu,W., Li,Y., Cao,Z. and Zhang,Y.
    PARL regulates porcine oocyte meiotic maturation by mediating mitochondrial activity
    Theriogenology (2025) 235, 75-85. PubMed  Europe PubMed DOI
    9. 2024
  9. Bach,K., Dohnalek,J., Skerlova,J., Kuzmik,J., Polachova,E., Stanchev,S., Majer,P., Fanfrlik,J., Pecina,A., Rezac,J., Lepsik,M., Borshchevskiy,V., Polovinkin,V. and Strisovsky,K.
    Extensive targeting of chemical space at the prime side of ketoamide inhibitors of rhomboid proteases by branched substituents empowers their selectivity and potency
    Eur J Med Chem (2024) 275, 116606-116606. PubMed  Europe PubMed DOI
  10. Ji,S., Bach,K., Miriyala,V.M., Dohnalek,J., Riopedre-Fernandez,M., Lepsik,M., van de Plassche,M., Vanhoutte,R., Barniol-Xicota,M., Moreira,R., Strisovsky,K. and Verhelst,S.H.L.
    4-Oxo-beta-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL
    ACS Med Chem Lett (2024) 15, 2101-2106. PubMed  Europe PubMed DOI  PMC  EPMC  I
  11. Schumacher,S., Klose,L., Lambertz,J., Lutjohann,D., Biemann,R., Kuerten,S. and Fester,L.
    The mitochondrial protease PARL is required for spermatogenesis
    Commun Biol (2024) 7, 44-44. PubMed  Europe PubMed DOI  PMC  EPMC
    12. 2023
  12. Radaelli,E., Assenmacher,C.A., Verrelle,J., Banerjee,E., Manero,F., Khiati,S., Girona,A., Lopez-Lluch,G., Navas,P. and Spinazzi,M.
    Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis
    elife (2023) 12 PubMed  Europe PubMed DOI  PMC  EPMC
    13. 2022
  13. Siebert,V., Silber,M., Heuten,E., Muhle-Goll,C. and Lemberg,M.K.
    Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state
    J Biol Chem (2022) 298, 102321-102321. PubMed  Europe PubMed DOI  PMC  EPMC
    14. 2021
  14. Anzmann,A.F., Sniezek,O.L., Pado,A., Busa,V., Vaz,F.M., Kreimer,S.D., DeVine,L.R., Cole,R.N., Le,A., Kirsch,B.J., Claypool,S.M. and Vernon,H.J.
    Diverse mitochondrial abnormalities in a new cellular model of TAFFAZZIN deficiency are remediated by Cardiolipin-interacting small molecules
    J Biol Chem (2021) , 101005-101005. PubMed  Europe PubMed DOI
  15. Lysyk,L., Brassard,R., Arutyunova,E., Siebert,V., Jiang,Z., Takyi,E., Morrison,M., Young,H.S., Lemberg,M.K., O'Donoghue,A.J. and Lemieux,M.J.
    Insights into the catalytic properties of the mitochondrial rhomboid protease PARL
    J Biol Chem (2021) , 100383-100383. PubMed  Europe PubMed DOI
  16. Merhi,R., Kalyn,M., Zhu-Pawlowsky,A. and Ekker,M.
    Loss of parla Function Results in Inactivity, Olfactory Impairment, and Dopamine Neuron Loss in Zebrafish
    Biomedicines (2021) 9 PubMed  Europe PubMed DOI  PMC  EPMC
  17. Parsons,W.H., Rutland,N.T., Crainic,J.A., Cardozo,J.M., Chow,A.S., Andrews,C.L. and Sheehan,B.K.
    Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL
    Bioorg Med Chem Lett (2021) 49, 128290-128290. PubMed  Europe PubMed DOI  I
    18. 2020
  18. Lysyk,L., Brassard,R., Touret,N. and Lemieux,M.J.
    PARL Protease: a glimpse at intramembrane proteolysis in the inner mitochondrial membrane
    J Mol Biol (2020) PubMed  Europe PubMed DOI
    19. 2019
  19. Spinazzi,M., Radaelli,E., Horre,K., Arranz,A.M., Gounko,N.V., Agostinis,P., Maia,T.M., Impens,F., Morais,V.A., Lopez-Lluch,G., Serneels,L., Navas,P. and De Strooper,B.
    PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome
    Proc Natl Acad Sci U S A (2019) 116, 277-286. PubMed  Europe PubMed DOI  K
    20. 2018
  20. Saita,S., Tatsuta,T., Lampe,P.A., Konig,T., Ohba,Y. and Langer,T.
    PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria
    EMBO J (2018) 37, e97909-e97909. PubMed  Europe PubMed DOI
    21. 2017
  21. Ishihara,N. and Mihara,K.
    PARL paves the way to apoptosis
    Nat Cell Biol (2017) 19, 263-265. PubMed  Europe PubMed DOI
  22. Shi,G. and McQuibban,G.A.
    The mitochondrial rhomboid protease PARL is regulated by PDK2 to integrate mitochondrial quality control and metabolism
    Cell Rep (2017) 18, 1458-1472. PubMed  Europe PubMed DOI
    23. 2016
  23. Spinazzi,M. and De Strooper,B.
    PARL: The mitochondrial rhomboid protease
    Semin Cell Dev Biol (2016) 60, 19-28. PubMed  Europe PubMed DOI  V
  24. Wust,R., Maurer,B., Hauser,K., Woitalla,D., Sharma,M. and Kruger,R.
    Mutation analyses and association studies to assess the role of the presenilin-associated rhomboid-like gene in Parkinson's disease
    Neurobiol Aging (2016) 39, e13-e15. PubMed  Europe PubMed DOI  M
    25. 2015
  25. Meissner,C., Lorenz,H., Hehn,B. and Lemberg,M.K.
    Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy
    Autophagy (2015) 11, 1484-1498. PubMed  Europe PubMed DOI
    26. 2013
  26. Chan,E.Y. and McQuibban,G.A.
    The mitochondrial rhomboid protease: Its rise from obscurity to the pinnacle of disease-relevant genes
    Biochim Biophys Acta (2013) 1828, 2916-2925. PubMed  Europe PubMed DOI
  27. Yamano,K. and Youle,R.J.
    PINK1 is degraded through the N-end rule pathway
    Autophagy (2013) 9, 1758-1769. PubMed  Europe PubMed DOI
    28. 2012
  28. Sekine,S., Kanamaru,Y., Koike,M., Nishihara,A., Okada,M., Kinoshita,H., Kamiyama,M., Maruyama,J., Uchiyama,Y., Ishihara,N., Takeda,K. and Ichijo,H.
    Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5
    J Biol Chem (2012) 287, 34635-34645. PubMed  Europe PubMed DOI
  29. Urban,S.
    Mammalian rhomboid proteases
    [ISSN:978-0-12-407742-3] (2012) 3, 3573-3581. DOI
    30. 2011
  30. Deas,E., Plun-Favreau,H., Gandhi,S., Desmond,H., Kjaer,S., Loh,S.H., Renton,A.E., Harvey,R.J., Whitworth,A.J., Martins,L.M., Abramov,A.Y. and Wood,N.W.
    PINK1 cleavage at position A103 by the mitochondrial protease PARL
    Hum Mol Genet (2011) 20, 867-879. PubMed  Europe PubMed DOI
  31. Heinitz,S., Klein,C. and Djarmati,A.
    The p.S77N presenilin-associated rhomboid-like protein mutation is not a frequent cause of early-onset Parkinson's disease
    Mov Disord (2011) 26, 2441-2442. PubMed  Europe PubMed DOI  M
  32. Jeyaraju,D.V., McBride,H.M., Hill,R.B. and Pellegrini,L.
    Structural and mechanistic basis of Parl activity and regulation
    Cell Death Differ (2011) 18, 1531-1539. PubMed  Europe PubMed DOI
  33. McQuibban,G.A. and Bulman,D.E.
    The PARLance of Parkinson disease
    Autophagy (2011) 7, 790-792. PubMed  Europe PubMed DOI  V
  34. Meissner,C., Lorenz,H., Weihofen,A., Selkoe,D.J. and Lemberg,M.K.
    The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking
    J Neurochem (2011) 117, 856-867. PubMed  Europe PubMed DOI
  35. Rahman,M. and Kylsten,P.
    Rhomboid-7 over-expression results in Opa1-like processing and malfunctioning mitochondria
    Biochem Biophys Res Commun (2011) 414, 315-320. PubMed  Europe PubMed DOI
  36. Shi,G., Lee,J.R., Grimes,D.A., Racacho,L., Ye,D., Yang,H., Ross,O.A., Farrer,M., McQuibban,G.A. and Bulman,D.E.
    Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease
    Hum Mol Genet (2011) 20, 1966-1974. PubMed  Europe PubMed DOI  M
    37. 2010
  37. Civitarese,A.E., MacLean,P.S., Carling,S., Kerr-Bayles,L., McMillan,R.P., Pierce,A., Becker,T.C., Moro,C., Finlayson,J., Lefort,N., Newgard,C.B., Mandarino,L., Cefalu,W., Walder,K., Collier,G.R., Hulver,M.W., Smith,S.R. and Ravussin,E.
    Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL
    Cell Metab (2010) 11, 412-426. PubMed  Europe PubMed DOI
  38. Curran,J.E., Jowett,J.B., Abraham,L.J., Diepeveen,L.A., Elliott,K.S., Dyer,T.D., Kerr-Bayles,L.J., Johnson,M.P., Comuzzie,A.G., Moses,E.K., Walder,K.R., Collier,G.R., Blangero,J. and Kissebah,A.H.
    Genetic variation in PARL influences mitochondrial content
    Hum Genet (2010) 127, 183-190. PubMed  Europe PubMed DOI  PMC  EPMC  M
  39. Jin,S.M., Lazarou,M., Wang,C., Kane,L.A., Narendra,D.P. and Youle,R.J.
    Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL
    J Cell Biol (2010) 191, 933-942. PubMed  Europe PubMed DOI  PMC  EPMC
    40. 2009
  40. Hatunic,M., Stapleton,M., Hand,E., DeLong,C., Crowley,V.E. and Nolan,J.J.
    The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population
    Diabetes Res Clin Pract (2009) 83, 316-319. PubMed  Europe PubMed DOI  M
    41. 2008
  41. Chao,J.R., Parganas,E., Boyd,K., Hong,C.Y., Opferman,J.T. and Ihle,J.N.
    Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons
    Nature (2008) 452, 98-102. PubMed  Europe PubMed DOI
  42. Whitworth,A.J., Lee,J.R., Ho,V.M., Flick,R., Chowdhury,R. and McQuibban,G.A.
    Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin
    Dis Model Mech (2008) 1, 168-174. PubMed  Europe PubMed DOI  PMC  EPMC
    43. 2007
  43. Pellegrini,L. and Scorrano,L.
    A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis
    Cell Death Differ (2007) 14, 1275-1284. PubMed  Europe PubMed DOI
  44. Scorrano,L.
    Multiple functions of mitochondria-shaping proteins
    Novartis Found Symp (2007) 287, 47-55. PubMed  Europe PubMed  K
    45. 2006
  45. [YEAR:14-7-2006]Cipolat,S., Rudka,T., Hartmann,D., Costa,V., Serneels,L., Craessaerts,K., Metzger,K., Frezza,C., Annaert,W., D'Adamio,L., Derks,C., Dejaegere,T., Pellegrini,L., D'Hooge,R., Scorrano,L. and De Strooper,B.
    Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling
    Cell (14-7-2006) 126, 163-175. PubMed  Europe PubMed DOI
  46. [YEAR:14-7-2006]Gottlieb,E.
    OPA1 and PARL keep a lid on apoptosis
    Cell (14-7-2006) 126, 27-29. PubMed  Europe PubMed DOI
  47. Jeyaraju,D.V., Xu,L., Letellier,M.C., Bandaru,S., Zunino,R., Berg,E.A., McBride,H.M. and Pellegrini,L.
    Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology
    Proc Natl Acad Sci U S A (2006) 103, 18562-18567. PubMed  Europe PubMed DOI  PMC  EPMC
  48. [YEAR:23-5-2006]McQuibban,G.A., Lee,J.R., Zheng,L., Juusola,M. and Freeman,M.
    Normal mitochondrial dynamics requires Rhomboid-7 and affects Drosophila lifespan and neuronal function
    Curr Biol (23-5-2006) 16, 982-989. PubMed  Europe PubMed DOI  K
    49. 2005
  49. [YEAR:24-2-2005]Walder,K., Kerr-Bayles,L., Civitarese,A., Jowett,J., Curran,J., Elliott,K., Trevaskis,J., Bishara,N., Zimmet,P., Mandarino,L., Ravussin,E., Blangero,J., Kissebah,A. and Collier,G.R.
    The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes
    Diabetologia (24-2-2005) 48, 459-468. PubMed  Europe PubMed DOI
    50. 2004
  50. [YEAR:19-1-2004]Sik,A., Passer,B.J., Koonin,E.V. and Pellegrini,L.
    Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide
    J Biol Chem (19-1-2004) 279, 15323-15329. PubMed  Europe PubMed DOI
    51. 2001
  51. Pellegrini,L., Passer,B.J., Canelles,M., Lefterov,I., Ganjei,J.K., Fowlkes,B.J., Koonin,E.V. and D'Adamio,L.
    PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2
    J Alzheimers Dis (2001) 3, 181-190. PubMed  Europe PubMed

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