ArticlePLoS genetics2013
Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Tissue-specific roles of peroxisomes revealed by expression meta-analysis.Biology direct · 2024Pooled it
- Peroxisome-derived ether lipids regulate lysosomal exocytosis.The EMBO journal · 2026Article
- Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation.Biomolecules · 2024Article
- Identification of hub genes and their expression profiling for predicting buffalo (Bubalus bubalis) semen quality and fertility.Scientific reports · 2023Article
- Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Liver Regeneration-Related Genes of Nontumor Liver Tissues Predict the Prognosis of Patients with Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Article
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.Signal transduction and targeted therapy · 2021Article
- Sperm Lipid Markers of Male Fertility in Mammals.International journal of molecular sciences · 2021Review
- Large-scale sequencing of flatfish genomes provides insights into the polyphyletic origin of their specialized body plan.Nature genetics · 2021Article
- Acute kidney injury leading to CKD is associated with a persistence of metabolic dysfunction and hypertriglyceridemia.iScience · 2021Article
- Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division.International journal of molecular sciences · 2020Article
- Short-term inhibition of autophagy benefits pancreatic β-cells by augmenting ether lipids and peroxisomal function, and by countering depletion of n-3 polyunsaturated fatty acids after fat-feeding.Molecular metabolism · 2020Article
- Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias.Scientific reports · 2020Article
- Peroxisomal Metabolite and Cofactor Transport in Humans.Frontiers in cell and developmental biology · 2020Review
- Chemoproteomic Profiling of Acetanilide Herbicides Reveals Their Role in Inhibiting Fatty Acid Oxidation.ACS chemical biology · 2017Article
- Revisiting the intraperoxisomal pathway of mammalian PEX7.Scientific reports · 2015Article
- The similarity between N-terminal targeting signals for protein import into different organelles and its evolutionary relevance.Frontiers in physiology · 2015Review
- Import of proteins into the peroxisomal matrix.Frontiers in physiology · 2013Review
Corrections and comments
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Authors and funding
27 authors at 12 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisomes are subcellular organelles involved in lipid metabolic processes, including those of very-long-chain fatty acids and branched-chain fatty acids, among others. Peroxisome matrix proteins are synthesized in the cytoplasm. Targeting signals (PTS or peroxisomal targeting signal) at the C-terminus (PTS1) or N-terminus (PTS2) of peroxisomal matrix proteins mediate their import into the organelle. In the case of PTS2-containing proteins, the PTS2 signal is cleaved from the protein when transported into peroxisomes. The functional mechanism of PTS2 processing, however, is poorly understood. Previously we identified Tysnd1 (Trypsin domain containing 1) and biochemically characterized it as a peroxisomal cysteine endopeptidase that directly processes PTS2-containing prethiolase Acaa1 and PTS1-containing Acox1, Hsd17b4, and ScpX. The latter three enzymes are crucial components of the very-long-chain fatty acids β-oxidation pathway. To clarify the in vivo functions and physiological role of Tysnd1, we analyzed the phenotype of Tysnd1(-/-) mice. Male Tysnd1(-/-) mice are infertile, and the epididymal sperms lack the acrosomal cap. These phenotypic features are most likely the result of changes in the molecular species composition of choline and ethanolamine plasmalogens. Tysnd1(-/-) mice also developed liver dysfunctions when the phytanic acid precursor phytol was orally administered. Phyh and Agps are known PTS2-containing proteins, but were identified as novel Tysnd1 substrates. Loss of Tysnd1 interferes with the peroxisomal localization of Acaa1, Phyh, and Agps, which might cause the mild Zellweger syndrome spectrum-resembling phenotypes. Our data established that peroxisomal processing protease Tysnd1 is necessary to mediate the physiological functions of PTS2-containing substrates.
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