Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in beta-oxidation of fatty acids.
Peroxisomes play an important role in beta-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 beta-oxidation. Tysnd1 itself undergoes processing through the removal of the presumably inhibitory N-terminal fragment. Tysnd1 expression is induced by the proliferator-activated receptor alpha 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 beta-oxidation.
Kurochkin
Igor V
IV
Immunoinformatics Team, Advanced Genome Information Group, RIKEN Genomic Sciences Center, Yokohama, Kanagawa, Japan. igork@gsc.riken.jp.jp
Mizuno
Yumi
Y
Konagaya
Akihiko
A
Sakaki
Yoshiyuki
Y
Schönbach
Christian
C
Okazaki
Yasushi
Y
D000595:Amino Acid Sequence; D000818:Animals; D001629:Bezafibrate; D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005227:Fatty Acids; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D003546:Cysteine Endopeptidases; C518157:Tysnd1 protein, rat; D001629:Bezafibrate