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International Journal of Molecular... Jul 2021The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet... (Review)
Review
The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet accumulation to build the cellular environment essential for their intracellular survival. Thus, lipids are thought to be important for mycobacteria survival as well as for the invasion, parasitization, and proliferation within host cells. However, their physiological roles have not been fully elucidated. Recent studies have revealed that mycobacteria modulate the peroxisome proliferator-activated receptor (PPAR) signaling and utilize host-derived triacylglycerol (TAG) and cholesterol as both nutrient sources and evasion from the host immune system. In this review, we discuss recent findings that describe the activation of PPARs by mycobacterial infections and their role in determining the fate of bacilli by inducing lipid metabolism, anti-inflammatory function, and autophagy.
Topics: Animals; Autophagy; Cholesterol; Humans; Lipid Metabolism; Mycobacterium; Mycobacterium Infections; Peroxisome Proliferator-Activated Receptors; Signal Transduction
PubMed: 34299217
DOI: 10.3390/ijms22147597 -
Frontiers in Cell and Developmental... 2022Peroxisomes are present in eukaryotic cells and have essential roles in various biological processes. Plant peroxisomes proliferate by biosynthesis or division of... (Review)
Review
Peroxisomes are present in eukaryotic cells and have essential roles in various biological processes. Plant peroxisomes proliferate by biosynthesis or division of pre-existing peroxisomes, degrade, or replace metabolic enzymes, in response to developmental stages, environmental changes, or external stimuli. Defects of peroxisome functions and biogenesis alter a variety of biological processes and cause aberrant plant growth. Traditionally, peroxisomal function-based screening has been employed to isolate mutants that are defective in peroxisomal metabolism, such as lipid degradation and photorespiration. These analyses have revealed that the number, subcellular localization, and activity of peroxisomes are closely related to their efficient function, and the molecular mechanisms underlying peroxisome dynamics including organelle biogenesis, protein transport, and organelle interactions must be understood. Various approaches have been adopted to identify factors involved in peroxisome dynamics. With the development of imaging techniques and fluorescent proteins, peroxisome research has been accelerated. Image-based analyses provide intriguing results concerning the movement, morphology, and number of peroxisomes that were hard to obtain by other approaches. This review addresses image-based analysis of peroxisome dynamics in plants, especially and .
PubMed: 35592252
DOI: 10.3389/fcell.2022.883491 -
International Journal of Cancer Sep 2019Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to... (Review)
Review
Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator-activated receptor γ coactivator 1a (PGC-1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC-1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC-1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC-1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC-1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC-1α modulators. A better understanding of the elegant function of PGC-1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC-1α signaling.
Topics: Autophagy; Humans; Methylation; Mitochondria; Mitophagy; Neoplasms; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphorylation; Protein Conformation; Protein Processing, Post-Translational; Signal Transduction
PubMed: 30848477
DOI: 10.1002/ijc.32253 -
Biomedicines Oct 2023Peroxisome proliferator-activated receptors (PPARs) are a group of ligand-binding transcription factors with pivotal action in regulating pleiotropic signaling pathways... (Review)
Review
Peroxisome proliferator-activated receptors (PPARs) are a group of ligand-binding transcription factors with pivotal action in regulating pleiotropic signaling pathways of energetic metabolism, immune responses and cell proliferation and differentiation. A significant body of evidence indicates that the PPARα receptor is an important modulator of plasma lipid and lipoprotein metabolism, with pluripotent effects influencing the lipid and apolipoprotein cargo of both atherogenic and antiatherogenic lipoproteins and their functionality. Clinical evidence supports an important role of PPARα agonists (fibric acid derivatives) in the treatment of hypertriglyceridemia and/or low high-density lipoprotein (HDL) cholesterol levels, although the effects of clinical trials are contradictory and point to a reduction in the risk of nonfatal and fatal myocardial infarction events. In this manuscript, we provide an up-to-date critical review of the existing relevant literature.
PubMed: 37893070
DOI: 10.3390/biomedicines11102696 -
Hepatology (Baltimore, Md.) Feb 2021Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1α (PGC1α) is a key regulator of mitochondrial biogenesis and respiration. PGC1α is involved in...
PPARγ Coactivator-1α Suppresses Metastasis of Hepatocellular Carcinoma by Inhibiting Warburg Effect by PPARγ-Dependent WNT/β-Catenin/Pyruvate Dehydrogenase Kinase Isozyme 1 Axis.
BACKGROUND AND AIMS
Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1α (PGC1α) is a key regulator of mitochondrial biogenesis and respiration. PGC1α is involved in the carcinogenesis, progression, and metabolic state of cancer. However, its role in the progression of hepatocellular carcinoma (HCC) remains unclear.
APPROACH AND RESULTS
In this study, we observed that PGC1α was down-regulated in human HCC. A clinical study showed that low levels of PGC1α expression were correlated with poor survival, vascular invasion, and larger tumor size. PGC1α inhibited the migration and invasion of HCC cells with both in vitro experiments and in vivo mouse models. Mechanistically, PGC1α suppressed the Warburg effect through down-regulation of pyruvate dehydrogenase kinase isozyme 1 (PDK1) mediated by the WNT/β-catenin pathway, and inhibition of the WNT/β-catenin pathway was induced by activation of PPARγ.
CONCLUSIONS
Low levels of PGC1α expression indicate a poor prognosis for HCC patients. PGC1α suppresses HCC metastasis by inhibiting aerobic glycolysis through regulating the WNT/β-catenin/PDK1 axis, which depends on PPARγ. PGC1α is a potential factor for predicting prognosis and a therapeutic target for HCC patients.
Topics: Biomarkers, Tumor; Carcinogenesis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Liver; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; PPAR gamma; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Prognosis; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Warburg Effect, Oncologic; Wnt Signaling Pathway; Xenograft Model Antitumor Assays
PubMed: 32298475
DOI: 10.1002/hep.31280 -
The Plant Journal : For Cell and... Sep 2019Although peroxisomes play a key role in plant metabolism under both normal and stressful growth conditions, the impact of drought and heat stress on the peroxisomes...
Although peroxisomes play a key role in plant metabolism under both normal and stressful growth conditions, the impact of drought and heat stress on the peroxisomes remains unknown. Quinoa represents an informative system for dissecting the impact of abiotic stress on peroxisome proliferation because it is adapted to marginal environments. Here we determined the correlation of peroxisome abundance with physiological responses and yield under heat, drought and heat plus drought stresses in eight genotypes of quinoa. We found that all stresses caused a reduction in stomatal conductance and yield. Furthermore, H O content increased under drought and heat plus drought. Principal component analysis demonstrated that peroxisome abundance correlated positively with H O content in leaves and correlated negatively with yield. Pearson correlation coefficient for yield and peroxisome abundance (r = -0.59) was higher than for commonly used photosynthetic efficiency (r = 0.23), but comparable to those for classical stress indicators such as soil moisture content (r = 0.51) or stomatal conductance (r = 0.62). Our work established peroxisome abundance as a cellular sensor for measuring responses to heat and drought stress in the genetically diverse populations. As heat waves threaten agricultural productivity in arid climates, our findings will facilitate identification of genetic markers for improving yield of crops under extreme weather patterns.
Topics: Chenopodium quinoa; Crops, Agricultural; Droughts; Gene Expression Regulation, Plant; Heat-Shock Response; Hot Temperature; Hydrogen Peroxide; Peroxisomes; Photosynthesis; Phylogeny; Plant Stomata
PubMed: 31108001
DOI: 10.1111/tpj.14411 -
International Journal of Molecular... Jan 2021Peroxisome proliferator-activated receptors (PPARα, PPAR, and PPAR) belong to the transcription factor family, and they are highly expressed in all types of trophoblast... (Review)
Review
Peroxisome proliferator-activated receptors (PPARα, PPAR, and PPAR) belong to the transcription factor family, and they are highly expressed in all types of trophoblast during pregnancy. The present review discusses currently published papers that are related to the regulation of PPARs via lipid metabolism, glucose metabolism, and amino acid metabolism to affect trophoblast physiological conditions, including differentiation, maturation, secretion, fusion, proliferation, migration, and invasion. Recent pieces of evidence have proven that the dysfunctions of PPARs in trophoblast lead to several related pregnancy diseases such as recurrent miscarriage, preeclampsia, intrauterine growth restriction, and gestational diabetes mellitus. Moreover, the underlying mechanisms of PPARs in the control of these processes have been discussed as well. Finally, this review's purposes are to provide more knowledge about the role of PPARs in normal and disturbed pregnancy with trophoblast, so as to find PPAR ligands as a potential therapeutic target in the treatment and prevention of adverse pregnancy outcomes.
Topics: Animals; Female; Gene Expression Regulation; Humans; Peroxisome Proliferator-Activated Receptors; Pregnancy; Trophoblasts
PubMed: 33406768
DOI: 10.3390/ijms22010433 -
Translational Oncology Sep 2023Among cancers, gastric cancer (GC) ranks third globally in morbidity and mortality, particularly in East Asia. Natriuretic peptide receptor A (NPRA), a receptor for...
Among cancers, gastric cancer (GC) ranks third globally in morbidity and mortality, particularly in East Asia. Natriuretic peptide receptor A (NPRA), a receptor for guanylate cyclase, plays important roles in regulating water and sodium balance. Recent studies have suggested that NPRA is involved in tumorigenesis, but its role in GC development remains unclear. Herein, we showed that the expression level of NPRA was positively correlated with gastric tumor size and clinical stage. Patients with high NPRA expression had a lower five-year survival rate than those with low expression, and NPRA was identified as an independent predictor of GC prognosis. NPRA knockdown suppressed GC cell proliferation, migration and invasion. NPRA overexpression enhanced cell malignant behavior. Immunohistochemistry of collected tumor samples showed that tumors with high NPRA expression had higher peroxisome proliferator-activated receptor α (PPARα) levels. In vivo and in vitro studies showed that NPRA promotes fatty acid oxidation and tumor cell metastasis. Co-IP showed that NPRA binds to PPARα and prevents PPARα degradation. PPARα upregulation under NPRA protection activates arnitine palmitoyl transferase 1B (CPT1B) to promote fatty acid oxidation. In this study, new mechanisms by which NPRA promotes the development of GC and new regulatory mechanisms of PPARα were identified.
PubMed: 37418841
DOI: 10.1016/j.tranon.2023.101734 -
The Journal of Investigative Dermatology Nov 2023Sebaceous glands (SGs) are holocrine glands that produce sebum, which primarily contains lipids that help to maintain the barrier function of the skin. Dysregulated...
Sebaceous glands (SGs) are holocrine glands that produce sebum, which primarily contains lipids that help to maintain the barrier function of the skin. Dysregulated lipid production contributes to the progression of some diseases characterized by dry skin, including atopic dermatitis. Although the lipid production of SGs has been well-studied, few studies have assessed their role in skin immune responses. We found that SGs and sebocytes expressed IL-4 receptor and produced high levels of T helper 2-associated inflammatory mediators after IL-4 treatment, suggesting immunomodulatory effects. Galectin-12 is a lipogenic factor expressed in sebocytes that affects their differentiation and proliferation. Using galectin-12-knockdown sebocytes, we showed that galectin-12 regulated the immune response in cells exposed to IL-4 and promoted CCL26 expression by upregulating peroxisome proliferator-activated receptor-γ. Moreover, galectin-12 suppressed the expression of endoplasmic reticulum stress-response molecules, and CCL26 upregulation by IL-4 was reversed after sebocyte treatment with inducers of endoplasmic reticulum stress, suggesting that galectin-12 controls IL-4 signaling by suppressing endoplasmic reticulum stress. Using galectin-12-knockout mice, we showed that galectin-12 positively regulated the IL-4-induced enlargement of SGs and the development of an atopic dermatitis-like phenotype. Thus, galectin-12 regulates the skin immune response by promoting peroxisome proliferator-activated receptor-γ expression and suppressing endoplasmic reticulum stress in SGs.
PubMed: 37207806
DOI: 10.1016/j.jid.2023.03.1684 -
Nature Communications Sep 2021Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome,...
Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling. While glycolysis is suppressed by AURKA inhibition, we note an increase in the oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO), which was accompanied by an increase of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). Combining AURKA inhibitors with inhibitors of FAO extends overall survival in orthotopic GBM PDX models. Taken together, these data suggest that simultaneous targeting of oxidative metabolism and AURKAi might be a potential novel therapy against recalcitrant malignancies.
Topics: Aurora Kinase A; Cell Line, Tumor; Cell Proliferation; Fatty Acids; Glioblastoma; Glycolysis; Humans; PPAR alpha; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Proteomics; Signal Transduction; Transcriptome; Warburg Effect, Oncologic
PubMed: 34471141
DOI: 10.1038/s41467-021-25501-x