Overexpression of the Mitochondrial T3 Receptor Induces Skeletal Muscle Atrophy during Aging

Casas, François; Pessemesse, Laurence; Grandemange, Stéphanie; Seyer, Pascal; Baris, Olivier; Guéguen, Naïg; Ramonatxo, Christelle; Perrin, Florence E.; Fouret, Gilles; Lepourry, Laurence; Cabello, Gérard; Wrutniak‐Cabello, Chantal

doi:10.1371/journal.pone.0005631

Cited by 47 publications

(39 citation statements)

References 36 publications

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“…The primer pair for TRa utilized in this study recognizes also the two truncated forms p43 and p28 that are synthesized by alternative translational initiation (Wrutniak-Cabello et al 2001). While p43 acts as a mitochondrial transcription factor (Casas et al 2009), p28 seems to be involved in the early mitochondrial T 3 influence (Wrutniak-Cabello et al 2001). Our results confirm that in FaO cells, the level of mRNA transcripts for TRs is negligible when compared with that of the rat liver.…”

Section: Discussionsupporting

confidence: 73%

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

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Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-L-diiodothyronine (T 2 ), as well as 3,3 0 ,5-L-triiodothyronine (T 3 ), was able to both prevent and reverse hepatic steatosis in rats fed a high-fat diet, and this effect depends on a direct action of iodothyronines on the hepatocyte. However, the involvement of thyroid hormone receptors (TRs) in mediating the lipid-lowering effect of iodothyronines was not elucidated. In this study, we investigated the ability of T 2 and T 3 to reduce the lipid overloading using the rat hepatoma FaO cells defective for functional TRs. The absence of constitutive mRNA expression of both TRa1 and TRb1 in FaO cells was verified by RT-qPCR. To mimic the fatty liver condition, FaO cells were treated with a fatty acid mixture and then exposed to pharmacological doses of T 2 or T 3 for 24 h. Lipid accumulation, mRNA expression of the peroxisome proliferator-activated receptors (PPAR-a, -g, -d) the acyl-CoA oxidase (AOX), and the stearoyl CoA desaturase (SCD1), as well as fuel-stimulated O 2 consumption in intact cells, were evaluated. Lipid accumulation was associated with an increase in triacylglycerol content, PPARg mRNA expression, and a decrease in PPARd and SCD1 mRNA expression. The addition of T 2 or T 3 to lipid-overloaded cells resulted in i) reduction in lipid content; ii) downregulation of PPARa, PPARg, and AOX expression; iii) increase in PPARd expression; and iv) stimulation of mitochondrial uncoupling. These data demonstrate, for the first time, that in the hepatocyte, the lipid-lowering actions of both T 2 and T 3 are not mediated by TRs.

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Section: Discussionsupporting

confidence: 73%

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

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“…Protein levels of p43 increased transiently with cytochrome c during postnatal rat tongue development, supporting a role for p43 in regulating mitochondrial RNA synthesis in development [33]. Regulation of thyroid hormone signaling at the organelle level may allow for functional tuning in mitochondria; p43 overexpression in skeletal muscle led to an initial increase in mitochondrial mass in mice at 2 months of age, but triggered a dramatic drop at 23 months, likely due to oxidative damage secondary to p43’s direct overstimulation of OXPHOS [34]. …”

Section: The Nuclear Epigenome In Anterograde Signalingmentioning

confidence: 99%

Mitochondrial-epigenetic crosstalk in environmental toxicology

Weinhouse

2017

Toxicology

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Crosstalk between the nuclear epigenome and mitochondria, both in normal physiological function and in responses to environmental toxicant exposures, is a developing sub-field of interest in environmental and molecular toxicology. The majority (~99%) of mitochondrial proteins are encoded in the nuclear genome, so programmed communication among nuclear, cytoplasmic, and mitochondrial compartments is essential for maintaining cellular health. In this review, we will focus on correlative and mechanistic evidence for direct impacts of each system on the other, discuss demonstrated or potential crosstalk in the context of chemical insult, and highlight biological research questions for future study. We will first review the two main signaling systems: nuclear signaling to the mitochondria [anterograde signaling], best described in regulation of oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis in response to environmental signals received by the nucleus, and mitochondrial signals to the nucleus [retrograde signaling]. Both signaling systems can communicate intracellular energy needs or a need to compensate for dysfunction to maintain homeostasis, but both can also relay inappropriate signals in the presence of dysfunction in either system and contribute to adverse health outcomes. We will first review these two signaling systems and highlight known or biologically feasible epigenetic contributions to both, then briefly discuss the emerging field of epigenetic regulation of the mitochondrial genome, and finally discuss putative “crosstalk phenotypes”, including biological phenomena, such as caloric restriction, maintenance of stemness, and circadian rhythm, and states of disease or loss of function, such as cancer and aging, in which both the nuclear epigenome and mitochondria are strongly implicated.

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“…For example, several studies have reported no age-induced change in MuRF1 and atrogin-1 (7,26,89), while others showed an increased (1,9,10) or decreased (15,18) expression of these atrogenes. We observed a two-to threefold increase in both atrogin-1 and MuRF1 mRNA in aged rats, which was associated with a concomitant stimulation of in vitro-determined proteasome activity.…”

Section: R892 Aging Alcohol and Muscle Protein Balancementioning

confidence: 99%

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Korzick

Sharda

Pruznak

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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The present study sought to determine whether the protein catabolic response in skeletal muscle produced by chronic alcohol feeding was exaggerated in aged rats. Adult (3 mo) and aged (18 mo) female F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% of total calories) or an isocaloric isonitrogenous control diet for 20 wk. Muscle (gastrocnemius) protein synthesis, as well as mTOR and proteasome activity did not differ between control-fed adult and aged rats, despite the increased TNF-α and IL-6 mRNA and decreased IGF-I mRNA in muscle of aged rats. Compared with alcohol-fed adult rats, aged rats demonstrated an exaggerated alcohol-induced reduction in lean body mass and protein synthesis (both sarcoplasmic and myofibrillar) in gastrocnemius. Alcohol-fed aged rats had enhanced dephosphorylation of 4E-BP1, as well as enhanced binding of raptor with both mTOR and Deptor, and a decreased binding of raptor with 4E-BP1. Alcohol feeding of both adult and aged rats reduced RagA binding to raptor. The LKB1-AMPK-REDD1 pathway was upregulated in gastrocnemius from alcohol-fed aged rats. These exaggerated alcohol-induced effects in aged rats were associated with a greater decrease in muscle but not circulating IGF-I, but no further increase in inflammatory mediators. In contrast, alcohol did not exaggerate the age-induced increase in atrogin-1 and MuRF1 mRNA or the increased proteasome activity. Our results demonstrate that, compared with adult rats, the gastrocnemius from aged rats is more sensitive to the catabolic effects of alcohol on protein synthesis, but not protein degradation, and this exaggerated response may be AMPK-dependent.

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Overexpression of the Mitochondrial T3 Receptor Induces Skeletal Muscle Atrophy during Aging

Cited by 47 publications

References 36 publications

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Mitochondrial-epigenetic crosstalk in environmental toxicology

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

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