The peroxisome derives its name from the fact that many metabolic enzymes that generate hydrogen peroxide as a by-product are sequestered here because peroxides are toxic to cells. Within peroxisomes, hydrogen peroxide is degraded by the enzyme catalase to water and oxygen. Peroxisomes are surrounded by a single membrane and they range in the diameter from 0.1 to 1 mm. They exist either in the form of a network of interconnected tubules (peroxisome reticulum), as in liver cells, or as individual micro peroxisomes in other cells such as tissue culture fibroblasts. 3
Functions of Peroxisomes
The principal function of peroxisomes is to house different metabolic pathways that are involved in various aspects of lipid metabolism. These include the following:
- Enzymes involved in the degradative oxidation (e.g., b-oxidation of very long chain fatty acids, 2-methyl-branched fatty acids, dicarboxylic acids, leukotrienes, bile acid intermediates and cholesterol side chains and both a- and b-oxidation of 3-methyl branched chain fatty acids)
- The synthesis of ether glycerolipids or plasmalogens.
- The formation of bile acids, dolichol, and cholesterol.
- The catabolism of purines, polyamines, and amino acids, and the detoxification of reactive oxygen species such as hydrogen peroxide, superoxide anions, and epoxides. In methylotrophic yeasts, peroxisomes are also involved in the metabolism of methanol and methylamines.
Biogenesis of Peroxisomes
As peroxisomes have no DNA, all their proteins must be imported from genes encoded in the nucleus. Most of the proteins that reside in the peroxisome matrix and membrane are synthesized in the cytosol and then imported posttranslationally to the organelle. About 25 PEX genes, encoding proteins called peroxins are necessary for the biogenesis of the organelle. Most of these genes are found in multiple organisms and 13 are conserved in humans
It's supposed that the early atmosphere of the earth had no oxygen. Somehow, it is claimed, anaerobe organisms which did not use oxygen for their metabolism evolved oxygenic photosynthesis. Molecular oxygen is toxic to obligate anaerobes organisms, and it is indispensable to the life of aerobes.
ROS Formation14Reactive oxygen species are formed by several different mechanisms:
- the interaction of ionizing radiation with biological molecules
- as an unavoidable byproduct of cellular respiration. Some electrons passing "down" the electron transport chain leak away from the main path (especially as they pass through complexes I and III) and go directly to reduce oxygen molecules to the superoxide anion (#2 above).
- synthesized by dedicated enzymes in phagocytic cells like neutrophils and macrophages
- NADPH oxidase (in both type of phagocytes)
- myeloperoxidase (in neutrophils only)
Defenses Against ROSCells have a variety of defenses against the harmful effects of ROS. These include two enzymes:
- superoxide dismutase (SOD), which converts two superoxide anions into a molecule of hydrogen peroxide and one of oxygen, an
as well as several small molecules that are antioxidants, such as
- alpha-tocopherol (vitamin E). This can break the covalent links that ROS have formed between fatty acid side chains in membrane lipids.
- uric acid. (Perhaps the long life span of some reptiles and birds is attributable to their high levels of uric acid.)vitamin C (in the right concentration)
ROS are EssentialBut it is important that the attempt to limit the production of ROS not succeed too well, because ROS have important functions to perform in the cell.
- The cells of the thyroid gland must make hydrogen peroxide in order to attach iodine atoms to thyroglobulin in the synthesis of thyroxine.
- Macrophages and neutrophils must generate ROS in order to kill some types of bacteria that they engulf by phagocytosis.
- Bacteria are engulfed into a phagosome.
- This fuses with a lysosome.Subunits of the enzyme NADPH oxidase assemble in the lysosome membrane forming the active enzyme.
- It catalyzes the synthesis of the superoxide anion.
- NADPH − 2 e− + 2O2 −> NADP+ + H+ + 2 . O2−This activity produces a large increase in oxygen consumption, called the "respiratory burst".
- Superoxide dismutase (SOD) converts this into hydrogen peroxide, which kills off the engulfed bacteria (except those that manufacture enough catalase to protect themselves).
Neutrophils (but not macrophages) also kill off engulfed pathogens by using the enzyme myeloperoxidase which catalyzes the reaction of hydrogen peroxide (made from superoxide anions) with chloride ions to produce the strongly antiseptic hypochlorite ion (OCl−, #6 above).
Signaling Functions of Reactive Oxygen Species 15
Among the reactive oxygen species, Hydrogen peroxide H2O2 best fulfills the requirements of being a second messenger. Its enzymatic production and degradation, along with the requirements for the oxidation of thiols by H2O2, provide the specificity for time and place that are required in signaling.
Reactive oxygen species (ROS) are produced in microorganisms as the unavoidable consequence of the aerobic life, by incomplete reduction of molecular oxygen during respiration (Imlay, 2003; Imlay, 2008; Imlay, 2013). Beside ROS, bacteria have to cope with many other redox-active compounds, including antimicrobials, antibiotics and environmental xenobiotics which can act as reactive electrophilic species (RES) and affect the cellular redox status (Jacobs & Marnett, 2010; Marnett et al, 2003). ROS and RES cause specific post-translational thiol-modifications in redox-sensing transcription factors which lead to conformational changes and activate or inactive the transcriptional regulator. As consequence, specific detoxification pathways are upregulated to destroy the reactive species or to repair the resulting damage (Antelmann & Helmann, 2011; Imlay, 2013; Vazquez-Torres, 2012). With the discovery of the peroxide-sensor OxyR of E. coli, it became evident that ROS-sensing by thiol-disulfide switches represents an important regulatory device in bacteria (Choi et al, 2001; Kim et al, 2002; Zheng et al, 1998). With the discovery of the peroxide-sensor OxyR of E. coli, it became evident that ROS-sensing by thiol-disulfide switches represents an important regulatory device in bacteria.
Reactive oxygen species as essential mediators of cell adhesion 16
Although superoxide anions (O2.−) and hydrogen peroxide (H2O2) are generally considered to be toxic by-products of respiration, recent evidence suggests that the production of these reactive oxygen species (ROS)* might be an integral component of membrane receptor signaling. In mammalian cells, a variety of extracellular stimuli have been shown recently to induce a transient increase in the intracellular concentration of ROS, and specific inhibition of the ROS generation results in a complete blockage of stimulant-dependent signaling (Gulati et al., 2001).
Data presented here lead to two major conclusions:
(a) ROS have a major role in the signaling cascade triggered by integrins during cell–ECM interaction; and
(b) modulation of integrin signaling and cell adhesion through FA formation by ROS is mediated, at least in part, by an up-regulation of FAK through an oxidative inhibition of LMW-PTP.
Researchers have long been puzzled as to how the cyanobacteria could make all that oxygen without poisoning themselves. To avoid their DNA getting wrecked by a hydroxyl radical that naturally occurs in the production of oxygen, the cyanobacteria would have had to evolve protective enzymes. But how could natural selection have led the cyanobacteria to evolve these enzymes if the need for them didn’t even exist yet? The explanations are fantasies at best.
Hydroxyl Radical (OH•)Among its family members, hydroxyl radical (OH•) is the most reactive and the most toxic ROS known. It is generated at neutral pH by the Fenton reaction between H2O2 and O•−2 catalyzed by transition metals like Fe (Fe2+, Fe3+). It has the capability to damage different cellular components by lipid peroxidation (LPO), protein damage and membrane destruction. Since there is no existing enzymatic system to scavenge this toxic radical, excess accumulation of OH• causes the cellular death (Pinto et al., 2003).
The highly toxic hydroxyl radical (OH•) is produced in the Fenton reaction by H2O2 and free ferrous iron (Fe2+) (Imlay, 2003; Imlay, 2008).
Nick Lane describes the dilemma in the book Oxygen, the molecule that made the world:
Before cells could commit to oxygenic photosynthesis, they must have learned to deal with its toxic waste, or they would surely have been killed, as modern anaerobes are today. But how could they adapt to oxygen if they were not yet producing it? An oxygen holocaust, followed by the emergence of a new world order, is the obvious answer; but we have seen that there is no geological evidence to favor such a catastrophic history. In terms of the traditional account of life on our planet, the difficulty and investment required to split water and produce oxygen is a Darwinian paradox.
The problem arises of how oxygenic photosynthesis could have evolved under these conditions. There were abundant reducing agents such as ferrous ion which made it unlikely that water would be used as an electron donor. It was suggested ‘that atmospheric hydrogen peroxide played a key role in inducing oxygenic photosynthesis because as peroxide increased in a local environment, organisms would not only be faced with a loss of reductant, but they would also be pressed to develop the biochemical apparatus (e.g., catalase) that would be ultimately be needed to protect against the products of oxygenic photosynthesis. This scenario allows for the early evolution of oxygen photosynthesis while global conditions were still anaerobic’ 10
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals). It catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS). Likewise, catalase has one of the highest turnover numbers of all enzymes; one catalase molecule can convert millions of hydrogen peroxide molecules to water and oxygen each second
The ancestral atmosphere without oxygen showed only poorly reducing character, and it probably contained predominantly carbon dioxide (CO2)
There are some geochemical and geophysical data, theoretical model considerations, molecular phylogenetic and biochemical comparative analyses that suggest a higher oxygenation of both the young Earth's surface and atmosphere than is commonly accepted. It has also been proposed that abiotically produced reactive oxygen species (ROS), such as H2O2, could be the primordial source of molecular oxygen (O2). This assumption has been supported by experiments that have shown that pyrite/aqueous suspensions generate H2O2 in the absence of O2.
We have formulated the following hypotheses: 2
(1) LUCA was not an obligate anaerobe, but it had genes that encoded enzymes that utilized ROS, for example, H2O2, and the earliest protocells were able to tolerate O2
(2) on the ancient surface of the young Earth, ca. 3.5 Ga, microenvironments could have existed where minor, but sufficient, amounts of ROS and O2 were generated in the generally anoxic environment of early Earth.
The presence of low concentrations of ROS, such as H2O2, and O2 should be taken into account in theoretical models of the early evolution of Archean oceans/atmosphere and life.
The obtained results might indicate that the ability of ROS detoxification did not emerge as a response to an increase in O2 level produced by cyanobacteria but that it was a crucial adaptation to weakly oxic (ROS) primordial microenvironments as a result of abiotic photochemical processes on early Earth.
The hypothesis concerning the occurrence of ROS-utilizing genes/enzymes and at least O2 tolerance by the first living organisms cannot be excluded and requires further study.
It was thus suggested ‘that atmospheric hydrogen peroxide played a key role in inducing oxygenic photosynthesis because as peroxide increased in a local environment, organisms would not only be faced with a loss of reductant, but they would also be pressed to develop the biochemical apparatus (e.g., catalase) that would be ultimately be needed to protect against the products of oxygenic photosynthesis.
Most likely LUCA possessed O2-and H2O2-involving pathways, mainly reactions to remove ROS, and had, at least in part, the components of aerobic respiration. 1
The role of the reactive oxygen species (ROS) family is that of a double-edged sword
while they act as secondary messengers in various key physiological phenomena, they also induce oxidative damages under several environmental stress conditions like salinity, drought, cold, heavy metals, UV irradiation etc., when the delicate balance between ROS production and elimination, necessary for normal cellular homeostasis, is disturbed. 11
In a biological context, ROS are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis 12
The cellular damages are manifested in the form of degradation of biomolecules like pigments, proteins, lipids, carbohydrates, and DNA, which ultimately amalgamate ( join, merge ) in plant cellular death. To ensure survival, plants have developed efficient antioxidant machinery.
1. enzymatic components like
superoxide dismutase (SOD),
ascorbate peroxidase (APX),
guaiacol peroxidase (GPX),
glutathione reductase (GR),
monodehydroascorbate reductase (MDHAR), and
dehydroascorbate reductase (DHAR);
2. non-enzymatic antioxidants like
ascorbic acid (AA),
reduced glutathione (GSH),
flavonoids, and the
These two components work hand in hand to scavenge ROS. In this review, we emphasize on the different types of ROS, their cellular production sites, their targets, and their scavenging mechanism mediated by both the branches of the antioxidant systems, highlighting the potential role of antioxidants in abiotic stress tolerance and cellular survival.
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling 17
Reactive oxygen species (ROS), such as superoxide anion (O2−), hydrogen peroxide (H2O2), and hydroxyl radical (HO•), consist of radical and non-radical oxygen species formed by the partial reduction of oxygen. Cellular ROS are generated endogenously as in the process of mitochondrial oxidative phosphorylation, or they may arise from interactions with exogenous sources such as xenobiotic compounds. When ROS overwhelm the cellular antioxidant defense system, whether through an increase in ROS levels or a decrease in the cellular antioxidant capacity, oxidative stress occurs. Oxidative stress results in direct or indirect ROS-mediated damage of nucleic acids, proteins, and lipids, and has been implicated in carcinogenesis , neurodegeneration [2,3], atherosclerosis, diabetes , and aging . However, ROS involvement in the pathogenesis of disease states is not confined to macromolecular damage. There is increasing evidence that ROS signaling contributes to disease. For example, ROS have been shown to promote tumor metastasis through gene activation . While there exists ample evidence demonstrating the role of ROS in regulating cellular signaling pathways, the question that is raised is exactly how do ROS initiate cellular signaling? The “oxidative interface” is that boundary between ROS and the signaling molecules they activate; that is, the figurative region that describes how ROS directly activate oxidative stress-responsive pathways.
Origin and evolution of the peroxisomal proteome 4
The presence of common protein import and organelle biogenesis systems support a single evolutionary origin. The precise scenario for this origin remains however to be established. Altogether our results indicate that the peroxisome does not have an endosymbiotic origin and that its proteins were recruited from pools existing within the primitive eukaryote.
So, basically another just-so superficial pseudo-scientific guesswork explanation !
The peroxisome is an essential eukaryotic organelle, crucial for lipid metabolism and free radical detoxification, development, differentiation, and morphogenesis from yeasts to humans. Loss of peroxisomes invariably leads to fatal peroxisome biogenesis disorders in man. The evolutionary origin of peroxisomes remains unsolved; proposals for either a symbiogenetic or cellular membrane invagination event are unconclusive. 8
Organelles can only be derived from a pre-existing organelle [1,2]. Gottfried Schatz referred to this rule as the ‘Third Genome’, written in a lipid alphabet in contrast to the First (nuclear DNA) and Second Genome (mitochondrial DNA) written in nucleotide letters. We are much less informed about how the delimiting membrane of an organelle is formed and enlarged compared to how proteins traffic within the cell and are sorted to their specific location. This is particularly true for peroxisomes. 9 We have a new concept of how peroxisomes are formed and maintained in the cell. Instead of being autonomous organelles that multiply by growth and division, they are formed from the ER and are part of the endomembrane family of organelles. This has major implications for the formulation of scenarios how they arose during evolution. Although speculation is hampered by lack of knowledge about plausible selective principles and formation of the eukaryotic cell as a whole, prerequisite conditions have narrowed. Their formation must be tightly linked to the evolution of the endomembrane system and an endosymbiont origin can be excluded.
Most of these core proteins are evolutionarily related to the Endoplasmic Reticulum Assisted Decay pathway, suggesting an evolutionary origin of the peroxisomes from the endomembrane system. A common evolutionary origin of the Peroxisome and the ER was also proposed by Schluter and coworkers
Our findings demonstrate an essential role for mitochondria in the de novo generation of peroxisomes in mammalian cells. 6 This is consistent with emerging evolutionary theories positing that peroxisomes evolved after mitochondrial ancestors entered the archaebacterial host, contributing to the rise of the endomembrane system within eukaryotic cells. Our data show remarkable segregation of the core peroxisomal import machinery between two distinct organelles; the ER and mitochondria. This segregation would ensure that import competence is acquired only upon fusion between pre-peroxisomes (see model in figure below).
Once peroxisomes are formed, they proliferate primarily through growth and division cycles. The clearance of peroxisomes by pexophagy leads to the mitochondrial import of Pex3, allowing new cycles of de novo peroxisomal biogenesis to occur. Together, our findings provide a new mechanistic framework with which to understand the signals that regulate de novo peroxisomal biogenesis and its physiological importance in complex mammalian
Researchers at the University of Exeter have now discovered how two cell organelles -- called peroxisomes and the endoplasmic reticulum (ER) -- associate with each other at the molecular level and work together. This cooperation is crucial for the production of specific lipids, which are essential for the function of nerve cells and can protect cells from oxidative damage. Loss of peroxisome function leads to a range of severe or fatal disorders associated with developmental and neurological defects. 7
Peroxisomal-protein import: is it really that complex?
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