Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Abstract

Modification of mitochondrial content demands the synthesis of hundreds of proteins encoded by nuclear and mitochondrial genomes. The responsibility for coordination of this process falls to nuclear-encoded master regulators of transcription. DNAbinding proteins and coactivators integrate information from energy-sensing pathways and hormones to alter mitochondrial gene expression. In mammals, the signaling cascade for mitochondrial biogenesis can be described as follows: hormonal signals and energetic information are sensed by protein-modifying enzymes that in turn regulate the post-translational modification of transcription factors. Once activated, transcription-factor complexes form on promoter elements of many of the nuclear-encoded mitochondrial genes, recruiting proteins that remodel chromatin and initiate transcription. One master regulator in mammals, PGC-1␣, is well studied because of its role in determining the metabolic phenotype of muscles, but also due to its importance in mitochondria-related metabolic diseases. However, relatively little is known about the role of this pathway in other vertebrates. These uncertainties raise broader questions about the evolutionary origins of the pathway and its role in generating the diversity in muscle metabolic phenotypes seen in nature.Résumé : La modification du contenu mitochondrial nécessite la synthèse de centaines de protéines encodées par les génomes nucléaire et mitochondrial, la coordination de ce processus étant assurée par des maîtres régulateurs de la transcription codés par le génome nucléaire. Des protéines se liant à l'ADN et des coactivateurs intègrent l'information provenant de voies de détection de l'énergie et d'hormones pour ensuite modifier l'expression des gènes mitochondriaux. Chez les mammifères, la cascade de signalisation pour la biogénèse mitochondriale peut être décrite comme suit : des enzymes de modification de protéines détectent des signaux hormonaux et de l'information énergétique et régulent la modification post-traduction des facteurs de transcription. Une fois activés, des complexes de facteurs de transcription se forment sur des éléments promoteurs de nombreux gènes mitochondriaux à encodage nucléaire, recrutant des protéines qui remodèlent la chromatine et amorcent la transcription. Un des maîtres régulateurs chez les mammifères, le PGC-1␣, fait l'objet de nombreuses études en raison de son rôle dans la détermination du phénotype métabolique des muscles, mais aussi en raison de son importance dans les maladies métaboliques associées aux mitochondries. Les connaissances sur le rôle de cette voie chez d'autres vertébrés sont toutefois limitées. Ces incertitudes soulèvent des questions plus larges concernant les origines évolutives de cette voie et son rôle dans la production de la diversité de phénotypes métaboliques musculaires observée dans la nature. [Traduit par la Rédaction]

Adaptation and acclimation of aerobic exercise physiology in Lake Whitefish ecotypes (Coregonus clupeaformis)

“…We found consistent increases in the activity of mitochondrial enzymes in dwarf white muscle, which argues that “master regulators” of mitochondrial biogenesis may vary among ecotypes and suggests candidates for future studies (reviewed by Bremer et al. ). However, variation in individual protein coding genes may also be important; there is strong evidence for selection on the proximal promoter of the cytoplasmic MDH (Jeukens and Bernatchez ) and the coding regions of many metabolic enzymes (Renaut et al.…”

“…Wild dwarf fish generally express OXPHOS genes in white muscle at higher levels than normal fish (Derome et al 2006;; but see Derome et al 2008), but different subunits of the same enzyme complexes often had different expression patterns, making it difficult to predict the effects of transcriptional divergence on enzyme activity and mitochondrial function. We found consistent increases in the activity of mitochondrial enzymes in dwarf white muscle, which argues that "master regulators" of mitochondrial biogenesis may vary among ecotypes and suggests candidates for future studies (reviewed by Bremer et al 2014). However, variation in individual protein coding genes may also be important; there is strong evidence for selection on the proximal promoter of the cytoplasmic MDH (Jeukens and Bernatchez 2012) and the coding regions of many metabolic enzymes .…”

“…The activities of many OXPHOS enzyme complexes are also posttranscriptionally regulated, making it difficult to predict the effects of transcriptional variation on mitochondrial function (Suarez and Moyes ; Bremer et al. ). Next, not all physiological traits match predictions of increased aerobic capacity in dwarf whitefish, as gill surface area is larger in normal fish (Evans et al.…”

“…However, there remain uncertainties: patterns of gene expression among individual proteins within OXPHOS complexes, among complexes, and among replicate populations of Lake Whitefish are not consistent (Derome et al 2006. The activities of many OXPHOS enzyme complexes are also posttranscriptionally regulated, making it difficult to predict the effects of transcriptional variation on mitochondrial function (Suarez and Moyes 2012;Bremer et al 2014). Next, not all physiological traits match predictions of increased aerobic capacity in dwarf whitefish, as gill surface area is larger in normal fish (Evans et al 2013).…”

Combined effects of temperature changes and metal contamination at different levels of biological organization in yellow perch

“…Beck and Fuller (2012) showed that thermal stress induces a decrease in the reserve capacity of the mitochondria (also termed reserve respiratory capacity) in a white bass (Morone chrysops) cell line, which may lead to the development of pathophysiological conditions. In gilthead sea bream (Sparus aurata), thermal stress leads to perturbations of gene expression related to mitochondrial oxidative capacities including COX genes (Bremer et al, 2014), which may be a regulatory response to the temperature-induced increase of oxidative capacities (Bermejo-Nogales et al, 2014). Our study partly supports these reports, since although we reported a sharp temperature-induced decrease in the expression of the cco gene in our perch livers, the activity of the CCO enzyme which increased between 9 and 20˚C, supporting an increase in oxidative capacities, decreased at the higher temperature studied.…”