English summary
      
      There is an increasing trend in intensive aquaculture towards maximizing both fish growth and productivity with high densities, high energy diets and high feeding rates. However, due to the interest to improve control mechanisms and fish welfare, it is necessary to find new markers that evaluate aquaculture practices. In this sense, the use of mitochondrial markers of oxidative stress and lipotoxicity are an essential tool to evaluate the risks of fish welfare. It is important to stand out that each of these markers provides complement and integrative information of special interest when specific species, tissues and stressors are considered. One of these mechanisms is the mitochondrial chaperone of the heat shock protein 70 family (glucose regulated protein 75, GRP75/mortalin), that protects mitochondrial components from the reactive oxygen species (ROS). A second mechanism is carried out by the uncoupling proteins (UCP), a family of mitochondrial transporters that uncouple the oxidative phosphorylation through the net discharge of proton gradient and diminish ROS production in a fatty acid rich milieu. 
      Molecular characterization of gilthead sea bream (Sparus aurata) GRP75/mortalin and UCPs demonstrate a high conservation degree of structural features and evolutionary closely related families of proteins. For GRP75/mortalin, the high degree of amino acid similarity enables the use of heterologous antibodies for protein analysis. Conversely, measures of respiration uncoupling and production of specific antibodies were necessary for UCP1 and UCP3. 
      Functional analysis of GRP75/mortalin shows inducible expression pattern of liver transcripts in response to confinement stress and with low adaptation to culture conditions. Accordingly, high expression of GRP75/mortalin was found in acute and chronic confinement stress at the mRNA and protein level, and the magnitude of the response was in accordance with the intensity of the stressor. Likewise, the hepatic expression of GRP75/mortalin could be considered as an integrative measure of the general state of the animal and/or domestication degree. In fact, when two species with similar growth potential are compared, but a stressful behavior in the case of common dentex (Dentex dentex), it is observed that poorly adapted to culture conditions is associated to a high expression of hepatic GRP75/mortalin. Regarding UCPs functional analysis, UCP1 is primarily expressed in liver whereas UCP3 was detected in skeletal and cardiac muscles, and the expression was inversely correlated to the oxidative capacity of the tissue. Similarly, both UCP1 and UCP3 are specific-regulated through factors that direct or indirectly alters energy supply and lipid metabolism in general. So that, the results showed that hepatic UCP1 is under negative regulation related to the increase in energy demand (confinement stress) and the reduction of energy intake during the seasonal adaptation. Meanwhile, UCP1 expression levels increase with fat deposition that occurs with age, and less evident with a diet deficient in essential fatty acids (EFA). Also, UCP3 appears to be under positive regulation related to the redistribution of lipids towards the muscle (age, diet deficient in EFA and seasonal fattening). However, to examine the effects of ration size on the regulation of UCP3 juvenile fish were fed at three different levels: i) full ration until visual satiety (R100 group), ii) 70% of satiation (R70 group) and iii) 70% of satiation with two finishing weeks at the maintenance ration (R70-20 group). Ration size led to two different energy states. The thirty percent feed restriction improved fish performance, increasing feed conversion efficiency and circulating levels of insulin-like growth factor-I (IGF-I). Conversely, fish of the R70-20 group showed a catabolic state with low circulating levels of IGF-I in combination with increased circulating concentrations of growth hormone and free fatty acids. Regarding expression levels, UCP3 is constitutively expressed in white glycolytic muscle so that is rapidly inactive when the oxidative capacity is improved. However, in aerobic muscles, the compensatory mechanisms are theoretically less operative, and respiration uncoupling would match the oxidative defense system to protect the mitochondria against lipid-induced oxidative stress. 
      
      In summary, GRP75/mortalin serves as a mechanism of cellular protection while UCPs decrease the risk of lipotoxicity and both are part of the integrated response to reduce oxidative stress. They can therefore be used along with other mitochondrial proteins to set limits on aquaculture practice and particularly in the gilthead sea bream.