Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix

Kanji Okumoto, Yukari Kametani, Yukio Fujiki

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The molecular mechanisms underlying protein turnover and enzyme regulation in the peroxisomal matrix remain largely unknown. Trypsin domain-containing 1 (Tysnd1) and peroxisomal Lon protease (PsLon) are newly identified peroxisomal matrix proteins that harbor both a serine protease-like domain and a peroxisome-targeting signal 1 (PTS1) sequence. Tysnd1 processes several PTS1-containing proteins and cleaves N-terminal presequences from PTS2-containing protein precursors. Here we report that knockdown of Tysnd1, but not PsLon, resulted in accumulation of endogenous β-oxidation enzymes in their premature form. The protease activity of Tysnd1 was inactivated by intermolecular self-conversion of the 60-kDa form to 15- and 45-kDa chains, which were preferentially degraded by PsLon. Peroxisomal β-oxidation of a very long fatty acid was significantly decreased by knockdown of Tysnd1 and partially lowered by PsLon knockdown. Taken together, these data suggest that Tysnd1 is a key regulator of the peroxisomal β-oxidation pathway via proteolytic processing of β-oxidation enzymes. The proteolytic activity of oligomeric Tysnd1 is in turn controlled by self-cleavage of Tysnd1 and degradation of Tysnd1 cleavage products by PsLon.

Original languageEnglish
Pages (from-to)44367-44379
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number52
DOIs
Publication statusPublished - Dec 30 2011

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Protease La
Trypsin
Peptide Hydrolases
Fatty Acids
Oxidation
Peroxisomes
Enzymes
Proteins
Protein Precursors
Serine Proteases
Ports and harbors
Protein Sorting Signals

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix. / Okumoto, Kanji; Kametani, Yukari; Fujiki, Yukio.

In: Journal of Biological Chemistry, Vol. 286, No. 52, 30.12.2011, p. 44367-44379.

Research output: Contribution to journalArticle

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