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Journal of Integrative Plant Biology Jul 2019Plant peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways, including fatty acid β-oxidation,... (Review)
Review
Plant peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways, including fatty acid β-oxidation, photorespiration, and degradation of reactive oxygen species. The compartmentalization of metabolic pathways into peroxisomes is a strategy for organizing the metabolic network and improving pathway efficiency. An important prerequisite, however, is the exchange of metabolites between peroxisomes and other cell compartments. Since the first studies in the 1970s scientists contributed to understanding how solutes enter or leave this organelle. This review gives an overview about our current knowledge of the solute permeability of peroxisomal membranes described in plants, yeast, mammals and other eukaryotes. In general, peroxisomes contain in their bilayer membrane specific transporters for hydrophobic fatty acids (ABC transporter) and large cofactor molecules (carrier for ATP, NAD and CoA). Smaller solutes with molecular masses below 300-400 Da, like the organic acids malate, oxaloacetate, and 2-oxoglutarate, are shuttled via non-selective channels across the peroxisomal membrane. In comparison to yeast, human, mammals and other eukaryotes, the function of these known peroxisomal transporters and channels in plants are discussed in this review.
Topics: Fatty Acids; Membrane Transport Proteins; Oxidation-Reduction; Peroxisomes
PubMed: 30761734
DOI: 10.1111/jipb.12790 -
Advanced Science (Weinheim,... Jul 2023The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes...
The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome-deficient mouse models (Atoh1-Pex5 and Pax2-Pex5 ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency-mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1-Pex5 mice when compared to wild-type (WT) mice. However, the expression of large-conductance, voltage-, and Ca2 -activated K (BK) channels is less in Atoh1-Pex5 mice as compared to the WT mice, and the administration of activators of BK channels (NS-1619 and NS-11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome-related hearing diseases such as PBDs.
Topics: Mice; Animals; Large-Conductance Calcium-Activated Potassium Channels; Peroxisomes; Hair Cells, Auditory; Hearing Loss; Mice, Knockout; Mechanistic Target of Rapamycin Complex 1; Mammals
PubMed: 37171794
DOI: 10.1002/advs.202300402 -
Nature Communications Aug 2022Membrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles,...
Membrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles, MCSs remain largely unexplored during infections. Here, we design a targeted proteomics platform for measuring MCS proteins at all organelles simultaneously and define functional virus-driven MCS alterations by the ancient beta-herpesvirus human cytomegalovirus (HCMV). Integration with super-resolution microscopy and comparisons to herpes simplex virus (HSV-1), Influenza A, and beta-coronavirus HCoV-OC43 infections reveals time-sensitive contact regulation that allows switching anti- to pro-viral organelle functions. We uncover a stabilized mitochondria-ER encapsulation structure (MENC). As HCMV infection progresses, MENCs become the predominant mitochondria-ER contact phenotype and sequentially recruit the tethering partners VAP-B and PTPIP51, supporting virus production. However, premature ER-mitochondria tethering activates STING and interferon response, priming cells against infection. At peroxisomes, ACBD5-mediated ER contacts balance peroxisome proliferation versus membrane expansion, with ACBD5 impacting the titers of each virus tested.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Herpes Simplex; Herpesviridae Infections; Humans; Organelles; Peroxisomes; Viruses
PubMed: 35953480
DOI: 10.1038/s41467-022-32488-6 -
Biochemical Society Transactions Apr 2023The study of endoplasmic reticulum (ER)-mitochondria communication is a vast and expanding field with many novel developments in the past few years. In this mini-review,... (Review)
Review
The study of endoplasmic reticulum (ER)-mitochondria communication is a vast and expanding field with many novel developments in the past few years. In this mini-review, we focus on several recent publications that identify novel functions of tether complexes, in particular autophagy regulation and lipid droplet biogenesis. We review novel findings that shed light on the role of triple contacts between ER and mitochondria with peroxisomes or lipid droplets as the third player. We also summarize recent findings on the role of ER-mitochondria contacts in human neurodegenerative diseases, which implicate either enhanced or reduced ER-mitochondria contacts in neurodegeneration. Taken together, the discussed studies highlight the need for further research into the role of triple organelle contacts, as well as into the exact mechanisms of increased and decreased ER-mitochondria contacts in neurodegeneration.
Topics: Humans; Mitochondria; Endoplasmic Reticulum; Peroxisomes; Neurodegenerative Diseases; Autophagy
PubMed: 36892405
DOI: 10.1042/BST20221305 -
Cells Jul 2020Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid... (Review)
Review
Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acidsynthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations inperoxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linkedto metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-relateddisorders, revealing the significance of peroxisome metabolism in human health. Cancer is a diseasewith metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functionaleects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles,such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated thanit is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomesand the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential ofinactivating peroxisomes to target cancer metabolism, which may pave the way for more eectivecancer treatment.
Topics: Animals; Biosynthetic Pathways; Homeostasis; Humans; Models, Biological; Neoplasms; Peroxisomes; Reactive Oxygen Species
PubMed: 32674458
DOI: 10.3390/cells9071692 -
International Journal of Molecular... Jan 2020The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular... (Review)
Review
The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular homeostasis. Precisely how substrate selectivity is achieved, and how individual substrates are degraded during selective autophagy in response to both extracellular and intracellular cues is not well understood. The aim of this review is to highlight pexophagy, the autophagic degradation of peroxisomes, as a model for selective autophagy. Peroxisomes are dynamic organelles whose abundance is rapidly modulated in response to metabolic demands. Peroxisomes are routinely turned over by pexophagy for organelle quality control yet can also be degraded by pexophagy in response to external stimuli such as amino acid starvation or hypoxia. This review discusses the molecular machinery and regulatory mechanisms governing substrate selectivity during both quality-control pexophagy and pexophagy in response to external stimuli, in yeast and mammalian systems. We draw lessons from pexophagy to infer how the cell may coordinate the degradation of individual substrates by selective autophagy across different cellular cues.
Topics: Animals; Autophagy; Macroautophagy; Models, Theoretical; Peroxisomes
PubMed: 31963200
DOI: 10.3390/ijms21020578 -
Annals of Neurology Sep 2023Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune...
OBJECTIVE
Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a multiplatform strategy.
METHODS
Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods.
RESULTS
SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11β, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05).
INTERPRETATION
COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Neuroinflammatory Diseases; RNA, Viral; Peroxisomes; Brain
PubMed: 37190821
DOI: 10.1002/ana.26679 -
International Journal of Molecular... Apr 2020Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and... (Review)
Review
Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of ; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of , thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.
Topics: Animals; Dietary Supplements; Disease Susceptibility; Humans; Metabolic Syndrome; Metals; Peroxisome Proliferator-Activated Receptors; Peroxisomes; Trace Elements
PubMed: 32283758
DOI: 10.3390/ijms21072612 -
Biochimica Et Biophysica Acta.... Feb 2020The type-2 peroxisomal targeting signal (PTS2) is one of two peptide motifs destining soluble proteins for peroxisomes. This signal acts as amphiphilic α-helix exposing... (Review)
Review
The type-2 peroxisomal targeting signal (PTS2) is one of two peptide motifs destining soluble proteins for peroxisomes. This signal acts as amphiphilic α-helix exposing the side chains of all conserved residues to the same side. PTS2 motifs are recognized by a bipartite protein complex consisting of the receptor PEX7 and a co-receptor. Cargo-loaded receptor complexes are translocated across the peroxisomal membrane by a transient pore and inside peroxisomes, cargo proteins are released and processed in many, but not all species. The components of the bipartite receptor are re-exported into the cytosol by a ubiquitin-mediated and ATP-driven export mechanism. Structurally, PTS2 motifs resemble other N-terminal targeting signals, whereas the functional relation to the second peroxisomal targeting signal (PTS1) is unclear. Although only a few PTS2-carrying proteins are known in humans, subjects lacking a functional import mechanism for these proteins suffer from the severe inherited disease rhizomelic chondrodysplasia punctata.
Topics: Amino Acid Motifs; Chondrodysplasia Punctata, Rhizomelic; Humans; Membrane Proteins; Peroxisomal Targeting Signal 2 Receptor; Peroxisomes; Protein Domains; Protein Structure, Quaternary; Protein Transport
PubMed: 31751594
DOI: 10.1016/j.bbamcr.2019.118609 -
Annual Review of Analytical Chemistry... Jun 2022Cellular organelles are highly specialized compartments with distinct functions. With the increasing resolution of detection methods, it is becoming clearer that same... (Review)
Review
Cellular organelles are highly specialized compartments with distinct functions. With the increasing resolution of detection methods, it is becoming clearer that same organelles may have different functions or properties not only within different cell populations of a tissue but also within the same cell. Dysfunction or altered function affects the organelle itself and may also lead to malignancies or undesirable cell death. To understand cellular function or dysfunction, it is therefore necessary to analyze cellular components at the single-organelle level. Here, we review the recent advances in analyzing cellular function at single-organelle resolution using high-parameter flow cytometry or multicolor confocal microscopy. We focus on the analysis of mitochondria, as they are organelles at the crossroads of various cellular signaling pathways and functions. However, most of the applied methods/technologies are transferable to any other organelle, such as the endoplasmic reticulum, lysosomes, or peroxisomes.
Topics: Endoplasmic Reticulum; Lysosomes; Microscopy, Confocal; Mitochondria; Peroxisomes
PubMed: 35303775
DOI: 10.1146/annurev-anchem-061020-111722