title: Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix.
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.
authors: Department of Biology, Faculty of Sciences, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors: Kanji
authors: K
authors: Okumoto
authors: Yukari
authors: Y
authors: Kametani
authors: Yukio
authors: Y
authors: Fujiki
mesh_terms: D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000201:enzymology* / Q000235:genetics; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012697:Serine Endopeptidases; D057057:Serine Proteases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; D005227:Fatty Acids; D021382:Protein Sorting Signals; C570302:PsLon protein, human; D057057:Serine Proteases; D012697:Serine Endopeptidases; C570301:Tysnd1 protein, human; D003546:Cysteine Endopeptidases