Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in β-oxidation of fatty acids

Igor V. Kurochkin, Yumi Mizuno, Akihiko Konagaya, Yoshiyuki Sakaki, Christian Schönbach, Yasushi Okazaki

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)835-845
Number of pages11
JournalEMBO Journal
Volume26
Issue number3
DOIs
Publication statusPublished - Feb 7 2007
Externally publishedYes

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Peptide Hydrolases
Fatty Acids
Oxidation
Peroxisomes
Enzymes
Protein Sorting Signals
Proteins
Processing
Bezafibrate
Substrates
Organelles
Cytosol
peroxisomal targeting signal 2 receptor

Keywords

  • Fatty acid oxidation
  • Peroxisomes
  • Protease
  • Protein processing
  • Tysnd1

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in β-oxidation of fatty acids. / Kurochkin, Igor V.; Mizuno, Yumi; Konagaya, Akihiko; Sakaki, Yoshiyuki; Schönbach, Christian; Okazaki, Yasushi.

In: EMBO Journal, Vol. 26, No. 3, 07.02.2007, p. 835-845.

Research output: Contribution to journalArticle

Kurochkin, Igor V. ; Mizuno, Yumi ; Konagaya, Akihiko ; Sakaki, Yoshiyuki ; Schönbach, Christian ; Okazaki, Yasushi. / Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in β-oxidation of fatty acids. In: EMBO Journal. 2007 ; Vol. 26, No. 3. pp. 835-845.
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