Alternative oxidase confers nutritional limitation on Drosophila development

Abstract

The mitochondrial alternative oxidase, AOX, present in most eukaryotes apart from vertebrates and insects, catalyzes the direct oxidation of ubiquinol by oxygen, by‐passing the terminal proton‐motive steps of the respiratory chain. Its physiological role is not fully understood, but it is proposed to buffer stresses in the respiratory chain similar to those encountered in mitochondrial diseases in humans. Previously, we found that the ubiquitous expression of AOX from Ciona intestinalis in Drosophila perturbs the development of flies cultured under low‐nutrient conditions (media containing only glucose and yeast). Here we tested the effects of a wide range of nutritional supplements on Drosophila development, to gain insight into the physiological mechanism underlying this developmental failure. On low‐nutrient medium, larvae contained decreased amounts of triglycerides, lactate, and pyruvate, irrespective of AOX expression. Complex food supplements, including treacle (molasses), restored normal development to AOX‐expressing flies, but many individual additives did not. Inhibition of AOX by treacle extract was excluded as a mechanism, since the supplement did not alter the enzymatic activity of AOX in vitro. Furthermore, antibiotics did not influence the organismal phenotype, indicating that commensal microbes were not involved. Fractionation of treacle identified a water‐soluble fraction with low solubility in ethanol, rich in lactate and tricarboxylic acid cycle intermediates, which contained the critical activity. We propose that the partial activation of AOX during metamorphosis impairs the efficient use of stored metabolites, resulting in developmental failure.

The Tardigrade Hypsibius Exemplaris as an Emerging Model to Study the Mitochondrial Alternative Oxidase at Animal Organismal Level

“…On the other hand, AOX a nity to its quinone substrate may increase under condition of the substrate prolonged reduction resulting from the blockage of the MRC complexes III and/or IV (e.g. [27]). However, in the case of H. exemplaris, the specimen activity and respiration are sensitive to BHAM also in the absence of MRC complex III and/or IV inhibition.…”

“…The rst one was studied in isolated C. gigas mitochondria [17] and after heterologous expression in the yeast Saccharomyces cerevisiae [18] cells [19]. The second one was heterologously expressed in mitochondria of cultured human cells [9,[20][21] as well as in the fruit y Drosophila (Sophophora) melanogaster [22] [23][24][25][26][27] and mouse [9,12,[28][29]. Additionally, some experimental data concerning AOX protein are available for crustaceans, the brine shrimp Artemia franciscana [30], the white shrimp Litopenaeus vannamei [31] [32] and the marine copepod Tigriopus californicus [33] [34].…”

The tardigradeHypsibius exemplarisas an emerging model to study the mitochondrial alternative oxidase at animal organismal level

“…On the other hand, AOX affinity to its quinone substrate may increase under condition of the substrate prolonged reduction resulting from the blockage of the MRC complexes III and/or IV (e.g. [27]). However, in the case of H. exemplaris, the specimen activity and respiration are sensitive to BHAM also in the absence of MRC complex III and/or IV inhibition.…”

“…The first one was studied in isolated C. gigas mitochondria [17] and after heterologous expression in the yeast Saccharomyces cerevisiae [18] cells [19]. The second one was heterologously expressed in mitochondria of cultured human cells [9,[20][21] as well as in the fruit fly Drosophila (Sophophora) melanogaster [22] [23][24][25][26][27] and mouse [9,12,[28][29]. Additionally, some experimental data concerning AOX protein are available for crustaceans, the brine shrimp Artemia franciscana [30], the white shrimp Litopenaeus vannamei [31] [32] and the marine copepod Tigriopus californicus [33] [34].…”

The tardigrade Hypsibius exemplaris has the active mitochondrial alternative oxidase that could be studied at animal organismal level

“…gigas mitochondria [ 15 ] and after heterologous expression in the yeast Saccharomyces cerevisiae cells [ 16 ]. The second one was heterologously expressed in mitochondria of cultured human cells [ 9 , 17 , 18 ] as well as in the fruit fly Drosophila (Sophophora) melanogaster [ 19 – 23 ] and mouse [ 9 , 12 , 24 , 25 ]. Additionally, some experimental data concerning AOX protein are available for crustaceans, the brine shrimp Artemia franciscana and the white shrimp Litopenaeus vannamei [ 26 ] and the marine copepod Tigriopus californicus [ 27 ].…”