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Redox Biology Jul 2020Catalase is a powerful antioxidant metalloenzyme located in peroxisomes which also plays a central role in signaling processes under physiological and adverse... (Review)
Review
Catalase is a powerful antioxidant metalloenzyme located in peroxisomes which also plays a central role in signaling processes under physiological and adverse situations. Whereas animals contain a single catalase gene, in plants this enzyme is encoded by a multigene family providing multiple isoenzymes whose number varies depending on the species, and their expression is regulated according to their tissue/organ distribution and the environmental conditions. This enzyme can be modulated by reactive oxygen and nitrogen species (ROS/RNS) as well as by hydrogen sulfide (HS). Catalase is the major protein undergoing Tyr-nitration [post-translational modification (PTM) promoted by RNS] during fruit ripening, but the enzyme from diverse sources is also susceptible to undergo other activity-modifying PTMs. Data on S-nitrosation and persulfidation of catalase from different plant origins are given and compared here with results from obese children where S-nitrosation of catalase occurs. The cysteine residues prone to be S-nitrosated in catalase from plants and from bovine liver have been identified. These evidences assign to peroxisomes a crucial statement in the signaling crossroads among relevant molecules (NO and HS), since catalase is allocated in these organelles. This review depicts a scenario where the regulation of catalase through PTMs, especially S-nitrosation and persulfidation, is highlighted.
Topics: Animals; Catalase; Cattle; Child; Humans; Hydrogen Sulfide; Nitric Oxide; Peroxisomes; Plants; Reactive Nitrogen Species
PubMed: 32505768
DOI: 10.1016/j.redox.2020.101525 -
Journal of Diabetes and Its... Mar 2021Pancreatic beta-cell lipo-dysfunction decreases insulin secretion and predisposes to the development of type 2 diabetes. Through targeted Pex11β knockdown and...
AIMS
Pancreatic beta-cell lipo-dysfunction decreases insulin secretion and predisposes to the development of type 2 diabetes. Through targeted Pex11β knockdown and peroxisome depletion, our aim was to investigate the specific contribution of peroxisomes to palmitate mediated pancreatic beta-cell dysfunction.
METHODS
MIN6 cells were transfected with probes targeted against Pex11β, a regulator of peroxisome abundance, or with scrambled control probes. Peroxisome abundance was measured by PMP-70 protein expression. 48 h post transfection, cells were incubated with 250 μM palmitate or BSA control for a further 48 h before measurement of glucose stimulated insulin secretion and of reactive oxygen species.
RESULTS
Pex11β knockdown decreased target gene expression by >80% compared with the scrambled control (P<0.001). This led to decreased PMP-70 expression (p<0.01) and a 22% decrease in peroxisome number (p<0.05). At 25 mM glucose, palmitate treatment decreased insulin secretion by 64% in the scrambled control cells (2.54±0.25 vs 7.07±0.83 [mean±SEM] ng/h/μg protein; Palmitate vs BSA P<0.001), but by just 37% in the Pex11β knockdown cells. Comparing responses in the presence of palmitate, insulin secretion at 25 mM glucose was significantly greater in the Pex11β knockdown cells compared with the scrambled controls (4.04±0.46 vs 2.54±0.25 ng/h/μg protein; p<0.05). Reactive oxygen species generation with palmitate was lower in the Pex11β knockdown cells compared with the scrambled controls (P<0.001).
CONCLUSION
Pex11β knockdown decreased peroxisome abundance, decreased palmitate mediated reactive oxygen species generation, and reversed the inhibitory effect of palmitate on insulin secretion. These findings reveal a distinct role of peroxisomes in palmitate mediated beta-cell dysfunction.
Topics: Animals; Cell Line; Diabetes Mellitus, Type 2; Gene Knockdown Techniques; Glucose; Insulin; Insulin-Secreting Cells; Membrane Proteins; Mice; Palmitates; Peroxisomes; Reactive Oxygen Species
PubMed: 33419633
DOI: 10.1016/j.jdiacomp.2020.107843 -
Journal of Cell Science Jun 2023Membrane contact sites are defined as regions of close proximity between two membranes; this association is mediated by protein-protein and/or protein-lipid... (Review)
Review
Membrane contact sites are defined as regions of close proximity between two membranes; this association is mediated by protein-protein and/or protein-lipid interactions. Contact sites are often involved in lipid transport, but also can perform other functions. Peroxisomal membrane contact sites have obtained little attention compared to those of other cell organelles. However, recent studies resulted in a big leap in our knowledge of the occurrence, composition and function of peroxisomal contact sites. Studies in yeast strongly contributed to this progress. In this Review, we present an overview of our current knowledge on peroxisomal membrane contact sites in various yeast species, including Hansenula polymorpha, Saccharomyces cerevisiae, Pichia pastoris and Yarrowia lipolytica. Yeast peroxisomes form contacts with almost all other cellular organelles and with the plasma membrane. The absence of a component of a yeast peroxisomal contact site complex results in a range of peroxisomal phenotypes, including metabolic and biogenesis defects and alterations in organelle number, size or position.
Topics: Saccharomyces cerevisiae; Peroxisomes; Mitochondrial Membranes; Biological Transport; Lipids; Fungal Proteins; Saccharomyces cerevisiae Proteins
PubMed: 37288671
DOI: 10.1242/jcs.259440 -
Cell Reports Oct 2023The enhanced response of glucagon and its Drosophila homolog, adipokinetic hormone (Akh), leads to high-caloric-diet-induced hyperglycemia across species. While previous...
The enhanced response of glucagon and its Drosophila homolog, adipokinetic hormone (Akh), leads to high-caloric-diet-induced hyperglycemia across species. While previous studies have characterized regulatory components transducing linear Akh signaling promoting carbohydrate production, the spatial elucidation of Akh action at the organelle level still remains largely unclear. In this study, we find that Akh phosphorylates extracellular signal-regulated kinase (ERK) and translocates it to peroxisome via calcium/calmodulin-dependent protein kinase II (CaMKII) cascade to increase carbohydrate production in the fat body, leading to hyperglycemia. The mechanisms include that ERK mediates fat body peroxisomal conversion of amino acids into carbohydrates for gluconeogenesis in response to Akh. Importantly, Akh receptor (AkhR) or ERK deficiency, importin-associated ERK retention from peroxisome, or peroxisome inactivation in the fat body sufficiently alleviates high-sugar-diet-induced hyperglycemia. We also observe mammalian glucagon-induced hepatic ERK peroxisomal translocation in diabetic subjects. Therefore, our results conclude that the Akh/glucagon-peroxisomal-ERK axis is a key spatial regulator of glycemic control.
Topics: Animals; Carbohydrates; Drosophila; Extracellular Signal-Regulated MAP Kinases; Glucagon; Glycemic Control; Hyperglycemia; Peroxisomes; Drosophila Proteins
PubMed: 37796662
DOI: 10.1016/j.celrep.2023.113200 -
Cells Sep 2022Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely...
Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation.
Topics: Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins; HeLa Cells; Humans; Macroautophagy; Nuclear Proteins; Peroxisomes; Reactive Oxygen Species; Transcription Factors
PubMed: 36139416
DOI: 10.3390/cells11182839 -
Trends in Microbiology Nov 2019Peroxisomes are multifunctional organelles with roles in cellular metabolism, cytotoxicity, and signaling. The plastic nature of these organelles allows them to respond... (Review)
Review
Peroxisomes are multifunctional organelles with roles in cellular metabolism, cytotoxicity, and signaling. The plastic nature of these organelles allows them to respond to diverse biological processes, such as virus infections, by remodeling their biogenesis, morphology, and composition to enhance specific functions. During virus infections in humans, peroxisomes act as important immune signaling organelles, aiding the host by orchestrating antiviral signaling. However, more recently it was discovered that peroxisomes can also benefit the virus, facilitating virus-host interactions that rewire peroxisomes to support cellular processes for virus replication and spread. Here, we describe recent studies that uncovered this double-edged character of peroxisomes during infection, highlighting mechanisms that viruses have coevolved to take advantage of peroxisome plasticity. We also provide a perspective for future studies by comparing the established roles of peroxisomes in plant infections and discussing the promise of virology studies as a venue to reveal the uncharted biology of peroxisomes.
Topics: Animals; Biological Evolution; Host Microbial Interactions; Humans; Peroxisomes; Plant Viruses; Viral Tropism; Virus Diseases; Virus Replication
PubMed: 31331665
DOI: 10.1016/j.tim.2019.06.006 -
Plant Physiology Apr 2021The life strategy of plants includes their ability to respond quickly at the cellular level to changes in their environment. The use of targeted fluorescent protein...
The life strategy of plants includes their ability to respond quickly at the cellular level to changes in their environment. The use of targeted fluorescent protein probes and imaging of living cells has revealed several rapidly induced organelle responses that create the efficient sub-cellular machinery for maintaining homeostasis in the plant cell. Several organelles, including plastids, mitochondria, and peroxisomes, extend and retract thin tubules that have been named stromules, matrixules, and peroxules, respectively. Here, I combine all these thin tubular forms under the common head of organelle extensions. All extensions change shape continuously and in their elongated form considerably increase organelle outreach into the surrounding cytoplasm. Their pleomorphy reflects their interactions with the dynamic endoplasmic reticulum and cytoskeletal elements. Here, using foundational images and time-lapse movies, and providing salient information on some molecular and biochemically characterized mutants with increased organelle extensions, I draw attention to their common role in maintaining homeostasis in plant cells.
Topics: Arabidopsis; Endoplasmic Reticulum; Homeostasis; Mitochondria; Peroxisomes; Plant Cells; Plastids
PubMed: 33793902
DOI: 10.1093/plphys/kiaa055 -
The Journal of Cell Biology May 2021Mitochondria, which are excluded from the secretory pathway, depend on lipid transport proteins for their lipid supply from the ER, where most lipids are synthesized. In...
Mitochondria, which are excluded from the secretory pathway, depend on lipid transport proteins for their lipid supply from the ER, where most lipids are synthesized. In yeast, the outer mitochondrial membrane GTPase Gem1 is an accessory factor of ERMES, an ER-mitochondria tethering complex that contains lipid transport domains and that functions, partially redundantly with Vps13, in lipid transfer between the two organelles. In metazoa, where VPS13, but not ERMES, is present, the Gem1 orthologue Miro was linked to mitochondrial dynamics but not to lipid transport. Here we show that Miro, including its peroxisome-enriched splice variant, recruits the lipid transport protein VPS13D, which in turn binds the ER in a VAP-dependent way and thus could provide a lipid conduit between the ER and mitochondria. These findings reveal a so far missing link between function(s) of Gem1/Miro in yeast and higher eukaryotes, where Miro is a Parkin substrate, with potential implications for Parkinson's disease pathogenesis.
Topics: Animals; Biological Transport; COS Cells; Cell Line; Cell Line, Tumor; Chlorocebus aethiops; Endoplasmic Reticulum; Eukaryota; GTP Phosphohydrolases; HeLa Cells; Humans; Mitochondria; Mitochondrial Dynamics; Parkinson Disease; Peroxisomes; Proteins; Ubiquitin-Protein Ligases
PubMed: 33891013
DOI: 10.1083/jcb.202010004 -
Molecular Cell Sep 2022Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal enzymes are imported from the cytosol by the receptor PEX5, which...
Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal enzymes are imported from the cytosol by the receptor PEX5, which interacts with a docking complex in the peroxisomal membrane and then returns to the cytosol after monoubiquitination by a membrane-embedded ubiquitin ligase. The mechanism by which PEX5 shuttles between cytosol and peroxisomes and releases cargo inside the lumen is unclear. Here, we use Xenopus egg extract to demonstrate that PEX5 accompanies cargo completely into the lumen, utilizing WxxxF/Y motifs near its N terminus that bind a lumenal domain of the docking complex. PEX5 recycling is initiated by an amphipathic helix that binds to the lumenal side of the ubiquitin ligase. The N terminus then emerges in the cytosol for monoubiquitination. Finally, PEX5 is extracted from the lumen, resulting in the unfolding of the receptor and cargo release. Our results reveal the unique mechanism by which PEX5 ferries proteins into peroxisomes.
Topics: Carrier Proteins; Humans; Ligases; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Protein Transport; Receptors, Cytoplasmic and Nuclear; Ubiquitin
PubMed: 35931083
DOI: 10.1016/j.molcel.2022.07.004 -
Annual Review of Cell and Developmental... Oct 2019Macroautophagy is an intracellular degradation system that delivers diverse cytoplasmic materials to lysosomes via autophagosomes. Recent advances have enabled... (Review)
Review
Macroautophagy is an intracellular degradation system that delivers diverse cytoplasmic materials to lysosomes via autophagosomes. Recent advances have enabled identification of several selective autophagy substrates and receptors, greatly expanding our understanding of the cellular functions of autophagy. In this review, we describe the diverse cellular functions of macroautophagy, including its essential contribution to metabolic adaptation and cellular homeostasis. We also discuss emerging findings on the mechanisms and functions of various types of selective autophagy.
Topics: Animals; Autophagosomes; Autophagy; Endoplasmic Reticulum; Homeostasis; Humans; Lysosomes; Mitochondria; Nutrients; Peroxisomes
PubMed: 31283377
DOI: 10.1146/annurev-cellbio-100818-125300