Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mummichog (Fundulus heteroclitus) has been shown to be responsive to peroxisome proliferating agents (PPAs). Peroxisomes function as important sites for fatty acid beta-oxidation. Peroxisome proliferation by PPAs or starvation can lead to changes in the size and number of peroxisomes and the expression of omega-hydroxylases (CYP2K1/2M1 in rainbow trout). Mummichogs were subjected to 96 h fasting or 96 h recovery from fasting. Expression of PMP70- and CYP2K1/2M1-like proteins in vehicle-treated or non-treated controls was compared in both males and females. Fasting and vehicle produced decreases in PMP70- and CYP2K1/2M1-like proteins in both males and females. In reproductive females, decreases due to fasting and vehicle treatment were greater than in female fish that were not gravid. Recovery from fasting resulted in levels of CYP2K1/2M1 near control levels in males while in recovered females, about 2-fold higher levels compared to controls were noted. These results indicate that gender, reproductive status and diet can produce changes in the expressed levels of peroxisomal PMP70 and microsomal CYP2K1/2M1-like proteins in the mummichog.
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PMID:Effects of vehicle, diet and gender on the expression of PMP70- and CYP2K1/2M1-like proteins in the mummichog. 1240 80

Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy. Expression of PEX2 leads to gross ubiquitination of peroxisomes and degradation of peroxisomes in an NBR1-dependent autophagic process. We identify PEX5 and PMP70 as substrates of PEX2 that are ubiquitinated during amino acid starvation. We also find that PEX2 expression is up-regulated during both amino acid starvation and rapamycin treatment, suggesting that the mTORC1 pathway regulates pexophagy by regulating PEX2 expression levels. Finally, we validate our findings in vivo using an animal model.
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PMID:PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. 2759 59

Peroxisomes are dynamic and multifunctional organelles involved in various cellular metabolic processes, and their numbers are tightly regulated by pexophagy, a selective degradation of peroxisomes through autophagy to maintain peroxisome homeostasis in cells. Catalase, a major peroxisome protein, plays a critical role in removing peroxisome-generated reactive oxygen species (ROS) produced by peroxisome enzymes, but the contribution of catalase to pexophagy has not been reported. Here, we investigated the role of catalase in peroxisome degradation during nutrient deprivation. Both short interfering RNA-mediated silencing of catalase and pharmacological inhibition by 3-aminotriazole (3AT) decreased the number of peroxisomes and resulted in the downregulation of peroxisomal proteins, such as PMP70 and PEX14 under serum starvation. In addition, treatment with 3AT induced NBR1-dependent autophagy and PEX5 ubiquitination in the absence of serum, which was accompanied by accumulation of ROS. Co-treatment with antioxidant agent N-acetyl-l-cysteine (NAC) prevented ROS accumulation and pexophagy by modulating peroxisome protein levels and the association of NBR1, a pexophagy receptor with peroxisomes. Taken together, these findings demonstrate that catalase plays an important role in pexophagy during nutrient deprivation.
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PMID:Catalase inhibition induces pexophagy through ROS accumulation. 2975 36