Oxygen concentrations in different environments.
Some 2.5 billion years ago, the great oxygenation event (GOE) led to a 105‐fold rise in atmospheric oxygen [O2], killing most species on Earth. In spite of the tendency to produce toxic reactive oxygen species (ROS), the highly exergonic reduction of O2 made it the ideal biological electron acceptor. During aerobic metabolism, O2 is reduced to water liberating energy, which is coupled to adenosine triphosphate (ATP) synthesis. Today, all organisms either aerobic or not need to deal with O2 toxicity. O2‐permeant organisms need to seek adequate [O2], for example, aquatic crustaceans bury themselves in the sea bottom where O2 is scarce. Also, the intestinal lumen and cytoplasm of eukaryotes is a microaerobic environment where many facultative bacteria or intracellular symbionts hide from oxygen. Organisms such as plants, fish, reptiles and mammals developed O2‐impermeable epithelia, plus specialized external respiratory systems in combination with O2‐binding proteins such as hemoglobin or leg‐hemoglobin control [O2] in tissues. Inside the cell, ROS production is prevented by rapid O2 consumption during the oxidative phosphorylation (OxPhos) of ATP. When ATP is in excess, OxPhos becomes uncoupled in an effort to continue eliminating O2. Branched respiratory chains, unspecific pores and uncoupling proteins (UCPs) uncouple OxPhos. One last line of resistance against ROS is deactivation by enzymes such as super oxide dismutase and catalase. Aerobic organisms profit from the high energy released by the reduction of O2, while at the same time they need to avoid the toxicity of ROS.
- oxidative stress
- adaptative metabolism
1. At the beginning, all life was anaerobic
The early Earth atmosphere contained high [H2], [NH3] and [CH4], while [O2] was less than 10-5 the present atmospheric level (PAL) [1, 2]. All life forms were anaerobic [3, 4]. Early redox reactions involved electron donors such as H2, CO2 or HS [5, 6], while electron acceptors were sulfur and NO3 . Eukaryotes were present before O2 rose [8, 9] and contained anaerobic mitochondrion‐like organelles [10, 11].
2. The massive increase in [O2] and the need to counteract its toxicity
Approximately 2.5 billion years ago, the great oxygenation event (GOE) was precipitated by both geological processes  and by the photosynthetic activity of cyanobacteria [13, 14]. Today, O2 is the preferred electron acceptor used by facultative microorganisms and the only one used by aerobes. The highly exergonic reduction of O2 provided the energy needed for the development of multicellular organisms. In addition, the high energy of activation required for O2 reduction ensures that this reaction occurs mostly through catalyzed reactions. For instance, oxidases bind their substrate tightly, preventing the liberation of reactive oxygen species (ROS) . At low concentrations, ROS are useful as signaling molecules, while at higher concentrations ROS damage and kill cells. Cells need much less [O2] than what is found in the atmosphere and thus, to prevent ROS production internal O2 is kept at a low level . Cells have developed two mechanisms to deal with surplus O2: (1) avoiding it and (2) rapidly reducing it. Furthermore, cellular O2 is found mostly bound to proteins such as hemoglobin, leg‐hemoglobin and myoglobin. Early oxy‐conformer organisms are permanent to O2, and thus, at different stages in their life cycle, they have to migrate to microaerobic or anaerobic spaces (Table 1) to cope with variations in O2. More evolved oxyregulator organisms from fish to mammals enveloped themselves in an O2‐impermeable epithelium, while at the same time developing highly specialized systems that control tissue [O2] (Figure 1). Oxyconformers and oxyregulators display different strategies to manage O2‐by‐product toxicity (Figure 1).
In oxyconformers, all cells are exposed to environmental [O2]. O2‐permeable organisms do have O2 transport proteins and intracellular O2‐binding proteins, but in addition, they need to implement diverse strategies to deal with changing O2. These include searching for microaerophilic or anaerobic environments. Arthropoda, the most abundant and widely distributed phylum on Earth, are oxyconformers ; it comprises subphyla Chelicerata (spiders), Myriapoda (centi‐ and millipedes), Hexapoda (Insects) and Crustacea, all of them protected by an exoskeleton. Nonaquatic insects possess a hard waterproof cuticle and branched invaginated tubules forming a specialized respiratory structure that works well at constant [O2]. Aquatic organisms, including most of the crustacea, are exposed to highly variant [O2], which may be 26 times lower than in the atmosphere [18, 19]. In water, [O2] varies with temperature, depth, mechanical aeration and tidal movements. Only few invertebrates (Plathelmynthes, Nematoda, Molluska, Anellida and Sypuncula) have been thoroughly studied in regard to their mechanisms to deal with fluctuating [O2] [20, 21]. Remarkably, very few studies on Crustacea are available.
|Environment||O2 concentration (μM)||References|
|1000m ASL 256.0|
Sea level 1028.0
|Minimal for coupling 0.1|
Minimal reported 20.0
MOZ < 20.0
In order to control the release of ROS oxyconformers reduce aerobic activity during hypoxia/ anoxia cycles, marine crustaceans display different responses to hypoxia/anoxia. To avoid hyperoxygenated or anoxic waters, crustaceans migrate between open sea and coastal lagoons (Figure 2), or migrate vertically through the water column to flee the O2‐minimum zone (OMZ) and into [O2] compatible with their metabolic needs [22, 23]. Some shrimp species, such as the burrowing thalassinids
Among unicellular organisms, diverse yeast species can survive at almost any [O2].
Many bacteria are facultative. Among these,
Obligate endosymbionts, such as
Many parasites exhibit various life‐cycle stages, which have different sensitivities to ROS engineered to endure attacks from macrophages.
In the bloodstream,
Malarial parasites are vulnerable to oxidative stress during their intraerythrocyte life stages. They contain the canonical respiratory chain (complex I, II, III and IV) plus an alternative electron transport pathway. Moreover, malarial mitochondria coordinate the biosynthesis of pyrimidine, heme and coenzyme Q .
Regardless the organism studied, cytoplasmic [O2] can vary widely, so damage control is needed at two levels. Either O2 is reduced independently of adenosine triphosphate (ATP) production in a process known as physiological uncoupling, or the ROS‐handling enzymes are activated. We shall briefly describe only physiological uncoupling as many reviews on ROS‐handling enzymes, such as superoxide dismutase and catalase are found elsewhere [42, 43].
3. Physiological uncoupling as an O2‐depleting mechanism and prevents ROS production
Both in oxyconformers and in oxyregulators, once O2 enters the cell it has to be reduced at a high rate. When ATP is needed the respiratory chain rapidly catalyzes this reduction. When there is energy surplus, O2 consumption has to be uncoupled from ATP synthesis with the aim of preventing ROS overproduction . A review on the physiological uncoupling mechanisms observed in mitochondria from different species of yeasts has been published recently . Yeast mitochondrial uncoupling mechanisms may be (a) proton sinks, such as the mitochondrial unspecific channels [46–48] and the uncoupling protein (UCP) [49, 50], or (b) nonpumping redox alternative enzymes found in branched respiratory chains [51–55].
Alternative oxidoreductases is the term designating all components of the respiratory chain different to the usual complexes I through IV. Most alternative oxidoreductases lack proton‐pumping activity and may coexist with, or substitute for the respiratory proton‐pumping complexes. Alternative enzymes catalyze the rapid, uncoupled flow of electrons towards O2. Alternative NADH dehydrogenases may either substitute for (
Alternative oxidases (AOXs) catalyze the oxidation of ubiquinol to quinone and the reduction of O2 to H2O in the absence of proton translocation . Although highly represented among plants, fungi and protist species, animal AOXs have been predicted to exist only in Molluska, Nematoda and Chordata . Recently, the number of phyla that probably possess AOX has increased including Placozoa, Porifera, Cnidaria, Annelida, Echinodermata, Hemichordata and Chordata. In some marine vertebrates, such as sipunculids, annelids (
Bacterial cytochrome‐containing oxidases are many. These enzymes are differentially expressed in response to different oxygen concentrations and on whether an organism is an obligate aerobic or a facultative species. In addition, oxidases may coexist depending on the species under study and they may play different roles in the cell . In
4. N‐fixating bacteria are a special case
Nitrogen‐fixating bacteria may be facultative as
5. ROS detoxification
In spite of the production‐prevention mechanisms outlined earlier, ROS may reach high concentrations, for example, during ischemia‐reperfusion. The last line of defense is detoxification. Enzymes such as superoxide dismutases (SODs) and catalases deactivate ROS. SODs have been grouped on the basis of the metal cofactor, which can be Fe, Mn, Ni or Cu/Zn . The Fe‐SODs are mostly found in microaerophiles and anaerobes. Microorganisms in aerobic environments prefer Mn‐SOD . Catalase dismutates hydrogen peroxide to water plus O2 . Several genes capable of H2O2 dismutation evolved from ancestral genomes. The most abundant was heme‐containing enzymes spread among bacteria, Archaea and Eukarya .
During the early paleoproterozoic period, a massive death toll resulted from a 105 times rise in atmospheric O2. In order to survive, organisms had to learn to cope with O2 toxicity while profiting from the large energy release coupled to its reduction. Several O2‐management strategies are revised here. Among these is hiding away from O2, moving to adequate O2 concentrations or excluding O2 with impermeable epithelia. Once O2 enters the cell, other mechanisms are designed to handle it. Its reactivity is controlled by O2‐quenching proteins or by rapidly reducing it with specific oxidases. In order to avoid side reactions, the rate of reduction had to be kept at optimal pace, independently of ATP production and thus several mechanisms of physiological uncoupling of oxidative phosphorylation evolved. Physiological uncoupling was achieved either by opening proton sinks or by using O2 independently of the proton gradient. Today, these mechanisms are expressed in many cells. Proton sinks include unspecific channels and uncoupling proteins, while proton gradient‐independent consumption of O2 involved alternative oxido‐reductases found in the branched respiratory chains of fungi, plants and arthropods. In spite of the function of all these O2‐management machines, O2 can still react unspecifically to form ROS, which destroy the cell through processes such as aging, apoptosis or necrosis. Once formed, ROS may still be eliminated by enzymes such as SOD and catalase, which are reviewed elsewhere  O2 is a great source of energy for the cell, but its high toxicity has to be dealt with, through mechanisms that we are only beginning to understand.
Authors thank Ramón Méndez‐Franco for technical assistance. Partially funded by the PAPIIT program and DGAPA/UNAM (grant IN202612). MRL, NLMG and CUA are CONACYT fellows enrolled in the Biochemistry Graduate Program at UNAM.