Elzbieta GlaserProfessor emerita
Research
Intracellular protein transport: signal peptides, molecular chaperones, proteolysis - connection to Alzheimer's disease.
Most of the mitochondrial and chloroplast proteins are nuclear encoded and synthesized as precursor proteins containing an N-terminal targeting peptide. After import, the targeting peptides are specifically cleaved off by the organellar processing peptidases. The cleaved targeting peptides are toxic to the organellar membranes and are rapidly degraded by a novel organellar peptidasome Presequence Protease (PreP), identified in our laboratory. We are using a combination of biochemical, molecular biological, biophysical and bioinformatic approaches to investigate different aspects of intracellular protein transport, such as sorting mechanisms, dual protein targeting, interaction of signal peptides with molecular chaperones and degradation of signal peptides by the PreP peptidasome. Furthermore, we are investigating the role of human mitochondrial PreP in Alzheimer´s disease as hPreP degrades amyloid-beta peptide forming insoluble fibers associated with Alzheimer´s disease.
Selected Recent Publications
- A multi-step peptidolytic cascade for amino acid recovery in chloroplasts. Teixeira PF, Kmiec B, Branca RM, Murcha MW, Byzia A, Ivanova A, Whelan J, Drag M, Lehtiö J, Glaser E. Nat Chem Biol. 2017 Jan;13(1):15-17. doi: 10.1038/nchembio.2227.
- Defective PITRM1 mitochondrial peptidase is associated with Aβ amyloidotic neurodegeneration. Brunetti D, Torsvik J, Dallabona C, Teixeira P, Sztromwasser P, Fernandez-Vizarra E, Cerutti R, Reyes A, Preziuso C, D'Amati G, Baruffini E, Goffrini P, Viscomi C, Ferrero I, Boman H, Telstad W, Johansson S, Glaser E, Knappskog PM, Zeviani M, Bindoff LA. EMBO Mol Med. 2015 Dec 23;8(3):176-90. doi: 10.15252/emmm.201505894.
- Shredding the signal: targeting peptide degradation in mitochondria and chloroplasts. Kmiec B, Teixeira PF, Glaser E. Trends Plant Sci. 2014 Dec;19(12):771-8. doi: 10.1016/j.tplants.2014.09.004. Epub 2014 Oct 7.
- Mechanism of oxidative inactivation of human presequence protease by hydrogen peroxide. Chen J, Teixeira PF, Glaser E, Levine RL. Free Radic Biol Med. 2014 Dec;77:57-63. doi: 10.1016/j.freeradbiomed.2014.08.016. Epub 2014 Sep 16.
- Interaction of the dual targeting peptide of Thr-tRNA synthetase with the chloroplastic receptor Toc34 in Arabidopsis thaliana. Ye W, Spånning E, Glaser E, Mäler L. FEBS Open Bio. 2015 Apr 30;5:405-12. doi: 10.1016/j.fob.2015.04.014. eCollection 2015.
- Protein import into plant mitochondria: signals, machinery, processing, and regulation. Murcha MW, Kmiec B, Kubiszewski-Jakubiak S, Teixeira PF, Glaser E, Whelan J. J Exp Bot. 2014 Dec;65(22):6301-35. doi: 10.1093/jxb/eru399. Epub 2014 Oct 16.
- Amyloid-β peptide induces mitochondrial dysfunction by inhibition of preprotein maturation. Mossmann D, Vögtle FN, Taskin AA, Teixeira PF, Ring J, Burkhart JM, Burger N, Pinho CM, Tadic J, Loreth D, Graff C, Metzger F, Sickmann A, Kretz O, Wiedemann N, Zahedi RP, Madeo F, Glaser E, Meisinger C. Cell Metab. 2014 Oct 7;20(4):662-9. doi: 10.1016/j.cmet.2014.07.024. Epub 2014 Aug 28.
- Mitochondrial import and degradation of amyloid-β peptide. Pinho CM, Teixeira PF, Glaser E. Biochim Biophys Acta. 2014 Jul;1837(7):1069-74. doi: 10.1016/j.bbabio.2014.02.007. Epub 2014 Feb 18.
- Import determinants of organelle-specific and dual targeting peptides of mitochondria and chloroplasts in Arabidopsis thaliana. Ge C, Spånning E, Glaser E, Wieslander A. Mol Plant. 2014 Jan;7(1):121-36. doi: 10.1093/mp/sst148. Epub 2013 Nov 8.
- Organellar oligopeptidase (OOP) provides a complementary pathway for targeting peptide degradation in mitochondria and chloroplasts. Kmiec B, Teixeira PF, Berntsson RP, Murcha MW, Branca RM, Radomiljac JD, Regberg J, Svensson LM, Bakali A, Langel U, Lehtiö J, Whelan J, Stenmark P, Glaser E. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):E3761-9. doi: 10.1073/pnas.1307637110. Epub 2013 Sep 16.
- Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related models. Hedskog L, Pinho CM, Filadi R, Rönnbäck A, Hertwig L, Wiehager B, Larssen P, Gellhaar S, Sandebring A, Westerlund M, Graff C, Winblad B, Galter D, Behbahani H, Pizzo P, Glaser E, Ankarcrona M. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7916-21. doi: 10.1073/pnas.1300677110. Epub 2013 Apr 25.
Funding Sources
The Swedish Research Council (VR-NT); Alzheimersfonden; Carl Tryggers Foundation; Fundação para a Ciência e a Tecnologia, Portugal