TY - JOUR
T1 - Comparative profiling of the peroxisomal proteome of wildtype and Pex7 knockout mice by quantitative mass spectrometry
AU - Wiese, Sebastian
AU - Gronemeyer, Thomas
AU - Brites, Pedro
AU - Ofman, Rob
AU - Bunse, Christian
AU - Renz, Christian
AU - Meyer, Helmut E.
AU - Wanders, Ronald J. A.
AU - Warscheid, Bettina
PY - 2012
Y1 - 2012
N2 - We present a label-free quantitative proteomic approach for the study of kidney peroxisomes of Pex7 knockout mice which is a bona-fide model for the human disease rhizomelic chondrodysplasia punctata (RCDP). RCDP is an autosomal recessive human disorder caused by mutations in the PEX7 gene encoding for Pex7, the cytosolic receptor protein that is essential for the import of proteins containing a functional peroxisomal targeting signal (PIS)-type 2. In this work, we quantitatively followed hundreds of proteins through high density gradient fractions of wildtype (WT) and Pex7 knockout (Pex7(-/-)) mice by high resolution mass spectrometry. A set of candidate proteins with altered abundance was defined via statistical and quantitative assessment of protein profiles obtained from WT and Pex7(-/-) mice. The results obtained demonstrate the feasibility of this approach to identify proteins specifically affected in abundance by the deletion of Pex7. All three known PTS2 proteins, including acetyl-Coenzyme A acyltransferase, alkylglycerone phosphate synthase and phytanoyl-CoA hydroxylase were determined to be virtually absent in these fractions whereas KIAA0564, a so far uncharacterized protein, was barely detectable in peroxisomal fractions of Pex7(-/-) mice. Furthermore, we report numerous PTS1 proteins with increased abundance levels in Pex7(-/-) mice that fulfill essential functions in the P-oxidation of very long-chain fatty acids or the biosynthesis of ether-phospholipids in peroxisomes. (C) 2011 Elsevier B.V. All rights reserved
AB - We present a label-free quantitative proteomic approach for the study of kidney peroxisomes of Pex7 knockout mice which is a bona-fide model for the human disease rhizomelic chondrodysplasia punctata (RCDP). RCDP is an autosomal recessive human disorder caused by mutations in the PEX7 gene encoding for Pex7, the cytosolic receptor protein that is essential for the import of proteins containing a functional peroxisomal targeting signal (PIS)-type 2. In this work, we quantitatively followed hundreds of proteins through high density gradient fractions of wildtype (WT) and Pex7 knockout (Pex7(-/-)) mice by high resolution mass spectrometry. A set of candidate proteins with altered abundance was defined via statistical and quantitative assessment of protein profiles obtained from WT and Pex7(-/-) mice. The results obtained demonstrate the feasibility of this approach to identify proteins specifically affected in abundance by the deletion of Pex7. All three known PTS2 proteins, including acetyl-Coenzyme A acyltransferase, alkylglycerone phosphate synthase and phytanoyl-CoA hydroxylase were determined to be virtually absent in these fractions whereas KIAA0564, a so far uncharacterized protein, was barely detectable in peroxisomal fractions of Pex7(-/-) mice. Furthermore, we report numerous PTS1 proteins with increased abundance levels in Pex7(-/-) mice that fulfill essential functions in the P-oxidation of very long-chain fatty acids or the biosynthesis of ether-phospholipids in peroxisomes. (C) 2011 Elsevier B.V. All rights reserved
U2 - https://doi.org/10.1016/j.ijms.2011.09.005
DO - https://doi.org/10.1016/j.ijms.2011.09.005
M3 - Article
SN - 0168-1176
VL - 312
SP - 30
EP - 40
JO - INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
JF - INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
ER -