Strategies of biochemical adaptation for hibernation in a South American marsupial, Dromiciops gliroides: 2. Control of the Akt pathway and protein translation machinery

Luu, Bryan E.; Wijenayake, Sanoji; Zhang, Jing; Tessier, Shannon N.; Gaitán‐Espitía, Juan Diego; Nespolo, Roberto F.; Storey, Kenneth B.

doi:10.1016/j.cbpb.2017.12.006

Cited by 16 publications

(13 citation statements)

References 42 publications

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“…A recent study that examined the regulation of the insulin signaling pathway across six different lemur tissues during torpor showed that were no changes to the levels of p-Akt (Ser-473) and only one out of six tissues (kidney) displayed a slight reduction in p-mTOR (Ser-2448) levels [ 51 ]. Similar trends were also observed in marsupials during daily torpor where no reduction in p-mTOR (Ser-2448) was evident but, surprisingly, levels of p-mTOR in liver were actually slightly elevated compared with the torpid state [ 52 ]. One possible explanation for such discrepancy in mTORC1 regulation amongst hibernators may be associated with the type of torpor.…”

Section: Mtorc1 Control Of Cell Growth Under Metabolic Stresssupporting

confidence: 70%

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mTOR Signaling in Metabolic Stress Adaptation

Storey

2021

Biomolecules

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The mechanistic target of rapamycin (mTOR) is a central regulator of cellular homeostasis that integrates environmental and nutrient signals to control cell growth and survival. Over the past two decades, extensive studies of mTOR have implicated the importance of this protein complex in regulating a broad range of metabolic functions, as well as its role in the progression of various human diseases. Recently, mTOR has emerged as a key signaling molecule in regulating animal entry into a hypometabolic state as a survival strategy in response to environmental stress. Here, we review current knowledge of the role that mTOR plays in contributing to natural hypometabolic states such as hibernation, estivation, hypoxia/anoxia tolerance, and dauer diapause. Studies across a diverse range of animal species reveal that mTOR exhibits unique regulatory patterns in an environmental stressor-dependent manner. We discuss how key signaling proteins within the mTOR signaling pathways are regulated in different animal models of stress, and describe how each of these regulations uniquely contribute to promoting animal survival in a hypometabolic state.

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Section: Mtorc1 Control Of Cell Growth Under Metabolic Stresssupporting

confidence: 70%

“…Phosphorylation (P) in green indicates the activation effect while phosphorylation in red indicates inhibitory effect. Data are summarized from the following studies: [ 15 , 16 , 17 , 18 , 19 , 46 , 51 , 52 ].…”

Section: Figurementioning

confidence: 99%

mTOR Signaling in Metabolic Stress Adaptation

Storey

2021

Biomolecules

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“…2e), suggesting that p53 is indeed functional. In bearded dragons, the oxidative stress response may be guided by the NF-κB stress response pathway; much like in mammalian hibernators [56][57][58][59] ( Fig. 5).…”

Section: Response To Cellular Stressmentioning

confidence: 99%

Waking the sleeping dragon: gene expression profiling reveals adaptive strategies of the hibernating reptile Pogona vitticeps

et al. 2019

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Background Hibernation is a physiological state exploited by many animals exposed to prolonged adverse environmental conditions associated with winter. Large changes in metabolism and cellular function occur, with many stress response pathways modulated to tolerate physiological challenges that might otherwise be lethal. Many studies have sought to elucidate the molecular mechanisms of mammalian hibernation, but detailed analyses are lacking in reptiles. Here we examine gene expression in the Australian central bearded dragon ( Pogona vitticeps ) using mRNA-seq and label-free quantitative mass spectrometry in matched brain, heart and skeletal muscle samples from animals at late hibernation, 2 days post-arousal and 2 months post-arousal. Results We identified differentially expressed genes in all tissues between hibernation and post-arousal time points; with 4264 differentially expressed genes in brain, 5340 differentially expressed genes in heart, and 5587 differentially expressed genes in skeletal muscle. Furthermore, we identified 2482 differentially expressed genes across all tissues. Proteomic analysis identified 743 proteins (58 differentially expressed) in brain, 535 (57 differentially expressed) in heart, and 337 (36 differentially expressed) in skeletal muscle. Tissue-specific analyses revealed enrichment of protective mechanisms in all tissues, including neuroprotective pathways in brain, cardiac hypertrophic processes in heart, and atrophy protective pathways in skeletal muscle. In all tissues stress response pathways were induced during hibernation, as well as evidence for gene expression regulation at transcription, translation and post-translation. Conclusions These results reveal critical stress response pathways and protective mechanisms that allow for maintenance of both tissue-specific function, and survival during hibernation in the central bearded dragon. Furthermore, we provide evidence for multiple levels of gene expression regulation during hibernation, particularly enrichment of miRNA-mediated translational repression machinery; a process that would allow for rapid and energy efficient reactivation of translation from mature mRNA molecules at arousal. This study is the first molecular investigation of its kind in a hibernating reptile, and identifies strategies not yet observed in other hibernators to cope stress associated with this remarkable state of metabolic depression. Electronic supplementary material The online version of this article (10.1186/s12864-019-5750-x) contains supplementary material, which is available to authorized users.

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“…However, the underlying metabolic origins and patterns of marsupial hibernation are unclear. We know of three published studies describing some functional aspects of marsupial hibernation (Franco, Contreras, & Nespolo, ; Hadj‐Moussa et al., ; Malan, ), which indicate some similarities with placental mammals (e.g., immunity suppression, mechanisms avoiding muscle atrophy, fuel switch to fat metabolism) but also some differences (e.g., a thermogenic role of the liver for rewarming and maintenance of the Akt metabolic pathway during torpor in the liver; Hadj‐Moussa et al., ; Luu et al., 2018a; Villarin, Schaeffer, Markle, & Lindstedt, ). In this study, we used RNA‐seq to analyse genomic‐wide expression patterns of central and peripheral organs in the South American marsupial Dromiciops gliroides .…”

Section: Introductionmentioning

confidence: 99%

“…For instance, D. gliroides seems to anticipate the cold season as a response to photoperiodic changes and thermal acclimation (Franco, Contreras, Place, Bozinovic, & Nespolo, ). In addition, several torpor‐regulation mechanisms were described in this species, including differential expression microRNAs (Hadj‐Moussa et al., ), implementation of the stress response through MAPK signalling (Luu et al., 2018b; Wijenayake et al., 2018a), reorganization of fuel use (Wijenayake et al., 2018b) and partial suppression of protein synthesis (Luu et al., 2018a). Here, we present a comprehensive transcriptomic analysis of torpid D. gliroides , providing the first explicit description of differentially regulated metabolic pathways of marsupial hibernation.…”

Section: Introductionmentioning

confidence: 99%

A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation

et al. 2018

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The small South American marsupial, Dromiciops gliroides, known as the missing link between the American and the Australian marsupials, is one of the few South American mammals known to hibernate. Expressing both daily torpor and seasonal hibernation, this species may provide crucial information about the mechanisms and the evolutionary origins of marsupial hibernation. Here, we compared torpid and active individuals, applying high-throughput sequencing technologies (RNA-seq) to profile gene expression in three D. gliroides tissues and determine whether hibernation induces tissue-specific differential gene expression. We found 566 transcripts that were significantly up-regulated during hibernation (369 in brain, 147 in liver and 50 in skeletal muscle) and 339 that were down-regulated (225 in brain, 79 in liver and 35 in muscle). The proteins encoded by these differentially expressed genes orchestrate multiple metabolic changes during hibernation, such as inhibition of angiogenesis, prevention of muscle disuse atrophy, fuel switch from carbohydrate to lipid metabolism, protection against reactive oxygen species and repair of damaged DNA.According to the global enrichment analysis, brain cells seem to differentially regulate a complex array of biological functions (e.g., cold sensitivity, circadian perception, stress response), whereas liver and muscle cells prioritize fuel switch and heat production for rewarming. Interestingly, transcripts of thioredoxin-interacting protein (TXNIP), a potent antioxidant, were significantly over-expressed during torpor in all three tissues. These results suggest that marsupial hibernation is a controlled process where selected metabolic pathways show adaptive modulation that can help to maintain homeostasis and enhance cytoprotection in the hypometabolic state.

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Strategies of biochemical adaptation for hibernation in a South American marsupial, Dromiciops gliroides: 2. Control of the Akt pathway and protein translation machinery

Cited by 16 publications

References 42 publications

mTOR Signaling in Metabolic Stress Adaptation

mTOR Signaling in Metabolic Stress Adaptation

Waking the sleeping dragon: gene expression profiling reveals adaptive strategies of the hibernating reptile Pogona vitticeps

A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation

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