Sensing and responding to energetic stress: The role of the AMPK-PGC1α-NRF1 axis in control of mitochondrial biogenesis in fish

Bremer, Katharina; Kocha, Katrinka M.; Snider, Trevor; Moyes, Christopher D.

doi:10.1016/j.cbpb.2015.09.005

Cited by 37 publications

(33 citation statements)

References 46 publications

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“…The obtained results are shown as means ± SD (*P < 0.05, **P < 0.01 vs both control cells). 29 Due to the increasing concentration of AMP in the cell, the active site (Thr172) of the AMPKα subunit is exposed. Of the two phosphorylation target residues, that is, Ser473 and Thr308, translocation of AKT kinase to mitochondria requires phosphorylation at Ser473 by MTORC2, 27 while for localization to the mitochondrial outer membrane and intermembrane space, Thr 308 must be phosphorylated by constitutively active PDK-1.…”

Section: Discussionmentioning

confidence: 99%

Activation of mammalian terget of rapamycin kinase and glycogen synthase kinase‐3β accompanies abnormal accumulation of cholesterol in fibroblasts from Niemann‐Pick type C patients

Woś

Komiażyk

Pikula

et al. 2018

J of Cellular Biochemistry

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Background Niemann Pick type C (NPC) lysosomal disorder is linked to the disruption of cholesterol transport. Recent data suggest that the molecular background of this disease is more complex. It was found that accumulation of cholesterol and glycolipids in the late endosomal/lysosomal compartment of NPC1 cells may affect mitochondrial functions. Materials and Methods In this study, primary skin fibroblasts derived from skin biopsies of two anonymous patients with NPC‐carrying mutations in the NPC1 gene, characterized by a high total cholesterol content, as well as two healthy donors were used. The presence of signaling proteins in the whole cell lysates and mitochondrial fractions were examined by Western blotting assay. Results In this report, we provide experimental evidence that in NPC1 cells, dysfunction of mitochondria and cellular metabolism, as reported by Wos et al in 2016, coexist with alterations in signal transduction pathways, such as the mammalian target of rapamycin, AKT, phosphoinositide‐dependent protein kinase‐1, glycogen synthase kinase‐3 β, and Jun amino‐terminal kinase, leading to abnormal cholesterol accumulation and distribution. Conclusion Differences in signal transduction between control and NPC1 cells may suggest that the latter cells experienced significant alterations in the complex molecular mechanisms that control cellular energy metabolism and vesicular transport.

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Section: Discussionmentioning

confidence: 99%

Activation of mammalian terget of rapamycin kinase and glycogen synthase kinase‐3β accompanies abnormal accumulation of cholesterol in fibroblasts from Niemann‐Pick type C patients

Woś

Komiażyk

Pikula

et al. 2018

J of Cellular Biochemistry

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“…Mitochondrial proliferation in cold-acclimated fish may be a response to an energetic shortfall, representing a means to maintain energy homeostasis despite the debilitating thermodynamic effects of cold. Cold acclimation in goldfish is accompanied by increases in AMP/ATP and ADP/ATP, consistent with energetic stress (Bremer et al, 2016). The capacity for adaptive remodelling of muscle energetics in response to physiological and environmental challenges is common amongst vertebrates, yet there are differences in the genetic mechanisms that regulate mitochondria gene expression in fish versus mammals (Bremer et al, 2012).…”

Section: Introductionmentioning

confidence: 86%

“…PGC-1α, which is critical to integration of transcriptional cascades in mammalian metabolism, differs in structure in ways that suggest a distinction in function. Fish PGC-1α has mutations in its NRF-1 binding domain (LeMoine et al, 2010) that appear to leave it incapable of binding NRF-1 (Bremer et al, 2016). Likewise, PGC-1α also lacks a site that is essential for regulation by AMPK (Bremer et al, 2016), which is a critical energy transducer in eukaryotes.…”

Section: Broader Implicationsmentioning

confidence: 99%

“…Fish PGC-1α has mutations in its NRF-1 binding domain (LeMoine et al, 2010) that appear to leave it incapable of binding NRF-1 (Bremer et al, 2016). Likewise, PGC-1α also lacks a site that is essential for regulation by AMPK (Bremer et al, 2016), which is a critical energy transducer in eukaryotes. While this may cast doubt on the role of PGC-1α as a master regulator of mitochondrial biogenesis in fish, it may well be that NRF-1 plays a similar role in fish and mammals, acting through a different coactivator such as PGC-1β.…”

Section: Broader Implicationsmentioning

confidence: 99%

“…In mammals, PGC-1α is important because of its ability to interact, directly or indirectly, with many DNA-binding proteins known to affect mitochondrial genes, including NRF-1 itself (Scarpulla, 2011). Although there may be differences in the PGC-1α axis in fish and mammals, owing to structural peculiarities in several regions of PGC-1α that bind NRF-1 (LeMoine et al, 2010;Bremer et al, 2016), it is likely that the suites of DNA-binding proteins that regulate oxidative genes in mammals perform similar functions in fish. In an analysis of the effects of thermal acclimation, we identified NRF-1 as a transcription factor that increases in parallel with the observed changes in COX4-1 mRNA (Bremer et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Evaluating the role of NRF-1 in regulation of the goldfish COX4-1 gene in response to temperature

Gao

Moyes

2016

Journal of Experimental Biology

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Cold acclimation in fish typically increases muscle mitochondrial enzymes. In mammals, stressors that increase mitochondrial content are mediated though transcriptional regulators, including nuclear respiratory factor-1 (NRF-1). Focusing on the goldfish gene for cytochrome c oxidase (COX) subunit 4-1, we analysed the regulatory regions in various contexts to identify a mechanistic link between NRF-1 and cold-induced mitochondrial proliferation. Promoter analysis implicated two putative NRF-1 sites: one in the proximal promoter and a second in exon 1, which encodes the 5′ untranslated region (5′-UTR). Transfection into mouse myoblasts showed that deletion of a region that included the proximal NRF-1 site reduced promoter activity by 30%; however, mutagenesis of the specific sequence had no effect. Thermal sensitivity analyses performed in rainbow trout gonadal fibroblasts (RTG-2) showed no effect of temperature (4 vs 19°C) on reporter gene expression. Likewise, reporters injected into muscle of thermally acclimated goldfish (4 vs 26°C) showed no elevation in expression. There was no difference in thermal responses of COX4-1 promoter reporters constructed from homologous regions of eurythermal goldfish and stenothermal zebrafish genes. NRF-1 chromatin immunoprecipitation of thermally acclimated goldfish muscle showed no temperature effect on NRF-1 binding to either the proximal promoter or 5′-UTR. It remains possible that the cold-induced upregulation of COX4-1 expression is a result of NRF-1 binding to distal regulatory regions or through indirect effects on other transcription factors. However, the proximal promoter does not appear to play a role in mediating the thermal response of the COX4-1 gene in fish.

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Metformin attenuates high-carbohydrate diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in Megalobrama amblycephala

Adjoumani,

Abasubong,

Zhang

et al. 2024

Fish Physiol Biochem

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Sensing and responding to energetic stress: The role of the AMPK-PGC1α-NRF1 axis in control of mitochondrial biogenesis in fish

Cited by 37 publications

References 46 publications

Activation of mammalian terget of rapamycin kinase and glycogen synthase kinase‐3β accompanies abnormal accumulation of cholesterol in fibroblasts from Niemann‐Pick type C patients

Activation of mammalian terget of rapamycin kinase and glycogen synthase kinase‐3β accompanies abnormal accumulation of cholesterol in fibroblasts from Niemann‐Pick type C patients

Evaluating the role of NRF-1 in regulation of the goldfish COX4-1 gene in response to temperature

Metformin attenuates high-carbohydrate diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in Megalobrama amblycephala

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