Effects of Defective in vivo Synthesis of Mitochondrial Proteins on Cellular Biochemistry and Physiology of Malnourished Rats

Abstract

Investigations were carried out to find the biochemical and bioenergetic implications of a defective in vivo synthesis of mitochondrial proteins during dietary-protein depletion. 3.4% dietary protein was fed to 21-day-old weanling rats for 30 days (experimental), while 21.0% dietary protein was fed to controls. A close simulation of marasmic-kwashiorkor syndrome was obtained in the experimental group. Rat liver mitochondria were isolated, and the functional and structural integrity was determined using biochemical standard parameters. Results show that the respiratory control ratio (RCR) is reduced by 50% in the experimental group, using any of the pyruvate/malate, β-hydroxybutyrate or succinate as substrate. The effects of storage at 0 °C were more pronounced in mitochondria from protein-depleted rats as these mitochondria are more leaky to protons (H⁺); hence they are defective in carrying out chemiosmotic oxidative phosphorylation. There is a drastic reduction in the basal ATPase and cytochrome oxidase activities with low ATP production and a decline in energy expenditure. This led to serious bioenergetic consequences culminating in heavy dependence on glycolysis and other biochemical aberrations.

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction

“…The PPARα induction of peroxisomal biogenesis and stimulation of mitochondrial FAO was sufficient to ameliorate hepatic steatosis and remarkably restore hepatic energy status and albumin synthesis suggesting a link between the peroxisomal and mitochondrial dysfunction, and liver health during malnutrition. Our study expands the understanding of early observations that suggested impairment of mitochondrial bioenergetic functions in livers of severely malnourished rats [30,31] and humans [32] and postulated a link between the loss of peroxisomal function and development of a fatty liver in severe malnutrition [33] Translating the animal model to the clinical phenotype of malnutrition Two clinical phenotypes of severe malnutrition exist. Marasmus is defined by clinical wasting, while kwashiorkor is typically accompanied by more complex characteristics such as 21 pitting edema, hair discoloration, skin lesions and hepatomegaly, although considerable overlap with marasmus often exists.…”

Dietary Nucleotides Modulate Mitochondrial Function of Intestinal Mucosa in Weanling Rats with Chronic Diarrhea

“…These authors reported a diminished respiratory control ratio and a drastic reduction in the basal enzymatic activities (such as ATPase and cytochrome c oxidase) with low ATP production in mitochondria of different tissues of protein-deficient rats. This led to bioenergetic consequences, such as dependence on glycolysis and other biochemical aberrations (6).…”

“…Digestion disorders with diarrheic symptoms are accompanied by altered redox and energetic mitochondrial processes. These impairments are evidenced by a reduced respiratory control ratio and changes in enzymatic activities, such as adenosine triphosphate synthase (ATPase), cytochrome oxidase, lactate dehydrogenase, succinate dehydrogenase, and alkaline phosphatase (5)(6)(7).…”

Redox Signaling from and to Peroxisomes: Progress, Challenges, and Prospects

“…Kwashiorkor, a disease caused by protein deficiency, has been associated with multiple adverse effects including -among others -hepatic steatosis, an almost total absence of peroxisomes, mitochondrial dysfunction, and oxidative stress (46,50,106,126). Recently, it was reported that feeding weanling rats a low protein diet yielded a similar phenotype, and that treating these animals with fenofibrate resulted in peroxisome reappearance, restoration of mitochondrial fitness, and amelioration of the hepatic phenotype (165).…”