Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.

Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system Nevertheless, substantial questions about the evolution of these mechanisms and control remain

https://people.clas.ufl.edu/devans/files/PRVGill.pdf

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

Cortisol is the principal corticosteriod in teleost fishes and its plasma concentrations rise dramatically during stress. The relationship between this cortisol increase and its metabolic consequences are subject to extensive debate. Much of this debate arises from the different responses of the many species used, the diversity of approaches to manipulate cortisol levels, and the sampling techniques and duration. Given the extreme differences in experimental approach, it is not surprising that inconsistencies exist within the literature. This review attempts to delineate common themes on the physiological and metabolic roles of cortisol in teleost fishes and to suggest new approaches that might overcome some of the inconsistencies on the role of this multifaceted hormone. We detail the dynamics of cortisol, especially the exogenous and endogenous factors modulating production, clearance and tissue availability of the hormone. We focus on the mechanisms of action, the biochemical and physiological impact, and the interaction with other hormones so as to provide a conceptual framework for cortisol under resting and/or stressed states. Interpretation of interactions between cortisol and other glucoregulatory hormones is hampered by the absence of adequate hormone quantification, resulting in correlative rather than causal relationships.

Cortisol in teleosts: dynamics, mechanisms of action, and metabolic regulation

Ammonia toxicity in fish

Uncoupling: new approaches to an old problem of bioenergetics

The migration of Arctic char Salvelinus alpinus from freshwater to seawater requires a substantial reorganization of the osmoregulatory tissues to regulate plasma ion levels. These modifications have an inherent metabolic cost, which must be met through the upregulation of intermediary metabolism. Arctic char intermediary metabolism was monitored during the initial 96 h of seawater acclimation through measurement of key enzymes in gill, liver, red and white muscle as well as tissue and blood free amino acid (FAA) levels, and plasma glucose and non-esterified fatty acid content. In general, seawater exposure stimulated large changes in amino acid metabolism, but no change in lipid or carbohydrate metabolism. White muscle FAA content increased significantly following seawater exposure, with levels of essential FAAs doubling after 96 h. Similar increases were seen in the plasma, suggesting a rapid mobilization of FAAs to the circulation. These changes were accompanied by significant increases in the activities of enzymes involved in amino acid metabolism in the gill, liver, red and white muscle, suggesting seawater-acclimated fish have an enhanced capacity for energy production from amino acids. Increased energy requirements were evident in the gill of seawater-acclimated char, as citrate synthase activity increased significantly. The results of this study suggest a rapid upregulation of amino acid metabolism may be critical for the successful acclimation of Arctic char to seawater.

Intermediary metabolism of Arctic char Salvelinus alpinus during short-term salinity exposure.

Glutamine synthetase (GSase), the enzyme that catalyses the conversion of glutamate and ammonia to glutamine, is present at high levels in vertebrate brain tissue and is thought to protect the brain from elevated ammonia concentrations. We tested the hypothesis that high brain GSase activity is critical in preventing accumulation of brain ammonia and glutamate during ammonia loading in the ammonia-intolerant rainbow trout. Trout pre-injected with saline or the GSase inhibitor methionine sulfoximine (MSOX, 6 mg kg(-1)), were exposed to 0, 670 or 1000 micromol l(-1) NH(4)Cl in the water for 24 and 96 h. Brain ammonia levels were 3- to 6-fold higher in ammonia-exposed fish relative to control fish and MSOX treatment did not alter this. Brain GSase activity was unaffected by ammonia exposure, while MSOX inhibited GSase activity by approximately 75%. Brain glutamate levels were lower and glutamine levels were higher in fish exposed to ammonia relative to controls. While MSOX treatment had little impact on brain glutamate, glutamine levels were significantly reduced by 96 h. With ammonia treatment, significant changes in the concentration of multiple other brain amino acids occurred and these changes were mostly reversed or eliminated with MSOX. Overall the changes in amino acid levels suggest that multiple enzymatic pathways can supply glutamate for the production of glutamine via GSase during ammonia exposure and that alternative transaminase pathways can be recruited for ammonia detoxification. Plasma cortisol levels increased 7- to 15-fold at 24 h in response to ammonia and MSOX did not exacerbate this stress response. These findings indicate that rainbow trout possess a relatively large reserve capacity for ammonia detoxification and for preventing glutamate accumulation during hyperammonaemic conditions.

Inhibition of glutamine synthetase during ammonia exposure in rainbow trout indicates a high reserve capacity to prevent brain ammonia toxicity

Measurements of key enzymes in several metabolic pathways in five tissues were undertaken in a freshwater elasmobranch, the dwarf stingray Potamotrygon magdalenae, with special emphasis on enzymes of lipid and ketone body oxidation. The metabolic organization of this freshwater elasmobranch resembles that of the marine elasmobranchs studied to date with some slight differences noted. As has been observed in marine elasmobranchs, lipid oxidation occurs largely in the liver. Other tissues, especially heart, may rely on the oxidation of other substrates, in particular amino acids. Amino acids appear to be very important metabolites for both oxidative and gluconeogenic tissues perhaps because of a reduced requirement for urea synthesis. Ketone bodies, especially beta-hydroxybutyrate, although less important in the freshwater elasmobranch than in marine forms, can be used by both marine and freshwater elasmobranchs, and this distinguishes them metabolically from all teleosts examined to date.

Absence of extrahepatic lipid oxidation in a freshwater elasmobranch, the dwarf stingray Potamotrygon magdalenae: Evidence from enzyme activities

The successful acclimation of eurhyhaline fishes from seawater to freshwater requires the gills to stop actively secreting ions and start actively absorbing ions. Gill Na+,K+‐ATPase is known to be an integral part of the active ion secretion model of marine fishes, but its importance in the active ion uptake model of freshwater fishes is less clear. This study, conducted in the high Arctic, examines gill Na+,K+‐ATPase regulation in wild anadromous arctic char returning to freshwater from the ocean. Gill Na+,K+‐ATPase activity, protein expression, and mRNA expression of Na+,K+‐ATPase isoforms α1a and α1b were monitored in arctic char at three points along their migration route to and from Somerset Island, Nunavut, Canada: out at sea (Whaler’s Point), in seawater near the river mouth (Nat’s Camp), and after entering the Union River. Arctic char collected from the Union River had more than twofold greater gill Na+,K+‐ATPase activity. This was associated with a significant increase (threefold) in Na+...

https://www.jstor.org/stable/10.1086/512982

Wild Arctic char (Salvelinus alpinus) upregulate gill Na+,K+-ATPase during freshwater migration.

Amino acid metabolism was examined in mitochondria from the lateral red muscle of a teleost (lake char, Salvelinus namaycush) and a nonteleost fish (bowfin, Amia calva). Isolated mitochondria oxidize a wide variety of substrates and have high respiratory control ratios. In both species, glutamine is oxidized more rapidly than any other amino acid. The rate of glutamine oxidation by bowfin mitochondria exceeds that of lake char mitochondria, and the bowfin displays correspondingly higher levels of mitochondrial phosphate-dependent glutaminase. It is suggested that amino acids in general, and glutamine in particular, are important oxidative substrates for nonteleost red muscle. The teleost red muscle, however, may rely on both glutamine and fatty acids as oxidative substrates. It appears that glutamate derived from glutamine is oxidized primarily via glutamate dehydrogenase, whereas exogenous glutamate is oxidized primarily via aspartate aminotransferase. Complete oxidation of glutamine may be accomplished in the absence of other substrates by conversion of glutamine-derived malate to pyruvate via malic enzyme. To assess the relative abilities of various tissues to synthesize and oxidize glutamine, the activities of glutamine synthetase and glutaminase were measured. The results of these studies indicate that the organization of glutamine metabolism of fish differs markedly from that in mammals.

James S. Ballantyne

Papers

Intermediary metabolism of Arctic char Salvelinus alpinus during short-term salinity exposure.

Inhibition of glutamine synthetase during ammonia exposure in rainbow trout indicates a high reserve capacity to prevent brain ammonia toxicity

Absence of extrahepatic lipid oxidation in a freshwater elasmobranch, the dwarf stingray Potamotrygon magdalenae: Evidence from enzyme activities

Wild Arctic char (Salvelinus alpinus) upregulate gill Na+,K+-ATPase during freshwater migration.

Glutamine metabolism in a holostean (Amia calva) and teleost fish (Salvelinus namaycush)