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Novel peroxisomal protease Tysnd1 processes PTS1‐ and PTS2‐containing enzymes involved in β‐oxidation of fatty acids
Author(s) -
Kurochkin Igor V,
Mizuno Yumi,
Konagaya Akihiko,
Sakaki Yoshiyuki,
Schönbach Christian,
Okazaki Yasushi
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601525
Subject(s) - peroxisome , peroxisomal targeting signal , biology , biochemistry , signal peptide , enzyme , cytosol , microbiology and biotechnology , peptide sequence , receptor , gene
Peroxisomes play an important role in β‐oxidation of fatty acids. All peroxisomal matrix proteins are synthesized in the cytosol and post‐translationally sorted to the organelle. Two distinct peroxisomal signal targeting sequences (PTSs), the C‐terminal PTS1 and the N‐terminal PTS2, have been defined. Import of precursor PTS2 proteins into the peroxisomes is accompanied by a proteolytic removal of the N‐terminal targeting sequence. Although the PTS1 signal is preserved upon translocation, many PTS1 proteins undergo a highly selective and limited cleavage. Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β‐oxidation. Tysnd1 itself undergoes processing through the removal of the presumably inhibitory N‐terminal fragment. Tysnd1 expression is induced by the proliferator‐activated receptor α agonist bezafibrate, along with the increase in its substrates. A model is proposed where the Tysnd1‐mediated processing of the peroxisomal enzymes promotes their assembly into a supramolecular complex to enhance the rate of β‐oxidation.