Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis

Fernández-Marcos, Pablo J.; Auwerx, Johan

doi:10.3945/ajcn.110.001917

Cited by 1,021 publications

(853 citation statements)

References 64 publications

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“…PGC-1α is the master regulator of mitochondrial biogenesis and energy expenditure (Fernandez-Marcos and Auwerx, 2011). The previous study using rat model reported that maternal high-fat intake led to a significant reduction in offspring hepatic PGC-1α mRNA expression (Burgueño et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Zou

et al. 2017

Animal

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Mitochondria plays an important role in the regulation of energy homeostasis. Moreover, mitochondrial biogenesis accompanies skeletal myogenesis, and we previously reported that maternal high-energy diet repressed skeletal myogenesis in pig fetuses. Therefore, the aim of this study was to evaluate the effects of moderately increased maternal energy intake on skeletal muscle mitochondrial biogenesis and function of the pig fetuses. Primiparous purebred Large White sows were allocated to a normal energy intake group (NE) as recommended by the National Research Council (NRC) and a high energy intake group (HE, 110% of NRC recommendations). On day 90 of gestation, fetal umbilical vein blood and longissimus (LM) muscle were collected. Results showed that the weight gain of sows fed HE diet was higher than NE sows on day 90 of gestation ( P < 0.05). Maternal HE diet increased fetal umbilical vein serum triglyceride and insulin concentrations ( P < 0.05), and tended to increase the homeostasis model assessment index ( P = 0.08). Furthermore, HE fetuses exhibited increased malondialdehyde concentration ( P < 0.05), and decreased activities of antioxidative enzymes ( P < 0.05) and intracellular NAD + level ( P < 0.05) in LM muscle. These alterations in metabolic traits of HE fetuses were accompanied by reduced mitochondrial DNA amount ( P < 0.05) and down-regulated messenger RNA expression levels of genes responsible for mitochondrial biogenesis and function ( P < 0.05). Our results suggest that moderately increased energy supply during gestation decreases mitochondrial biogenesis, function and antioxidative capacity in skeletal muscle of pig fetuses.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Zou

et al. 2017

Animal

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“…PGC-1a is a master transcription cofactor regulating mitochondrial biogenesis and function that is itself regulated by transcription and extensive posttranslational modifications 11,28 . Consistent with the dysfunction of the mitochondria, both mRNA and protein levels of PGC-1a are reduced in Wps/Wps BAT before the appearance of the obese phenotype (Fig.…”

Section: Scf/kit Expression Is Altered In Obese Animals and Humansmentioning

confidence: 99%

“…Peroxisome proliferatoractivated receptor-g (PPARg) coactivator-1a (PGC-1a, encoded by the Ppargc1a gene) has emerged as the master regulator of mitochondrial biogenesis and function 11 . PGC-1a activates mitochondrial biogenesis through stimulating mitochondrial transcription factor A (TFAM) and nuclear respiratory factors (NRFs), key regulators of mitochondrial DNA (mtDNA) replication/transcription 12 .…”

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confidence: 99%

The stem cell factor/Kit signalling pathway regulates mitochondrial function and energy expenditure

Huang

Ruan

et al. 2014

Nat Commun

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Cell growth is tightly coupled with mitochondrial biogenesis in order to maintain energy and organelle homeostasis. Receptor tyrosine kinase Kit and its ligand, stem cell factor (SCF), play a critical role in the growth and survival of multiple cell lineages. Here we report that the expression of SCF and Kit in adipose tissues is responsive to food availability and environmental temperature, and is altered in obese mice and human patients. Mice carrying a lossof-function mutation in Kit develop obesity as a result of decreased energy expenditure. These phenotypes are associated with reduced PGC-1a expression and mitochondrial dysfunction in brown adipose tissue and skeletal muscle. We further demonstrate that SCF/Kit directly promotes Ppargc1a transcription and mitochondrial biogenesis. Blocking Kit signalling in mice decreases PGC-1a expression and thermogenesis, while overexpressing SCF systemically or specifically in brown adipose tissue increases thermogenesis and reduces weight gain. Collectively, these data provide mechanistic insight into the regulation of mitochondrial function by SCF/Kit signalling and lay a foundation for exploring SCF/Kit signalling as a therapeutic target for metabolic diseases.

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“…At the same time, this research has uncovered new levels of complexity in transcriptional regulation mediated by PGC-1 coactivators. Of the three founding members of the family, PGC-1α has received the most attention, partly because of the many and highly regulated mechanisms that determine its activation and biological activity (comprehensively reviewed in [2,3]). More recently, work from several laboratories has shown that transcription of a single PGC-1α (also known as PPARGC1A) gene is controlled by several promoter regions that, coupled to alternative splicing, give rise to coactivator variants with distinct transcript and protein structure.…”

Section: Introductionmentioning

confidence: 99%

The hitchhiker’s guide to PGC-1α isoform structure and biological functions

2015

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Proteins of the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 (PGC-1) family of transcriptional coactivators coordinate physiological adaptations in many tissues, usually in response to demands for higher nutrient and energy supply. Of the founding members of the family, PGC-1α (also known as PPARGC1A) is the most highly regulated gene, using multiple promoters and alternative splicing to produce a growing number of coactivator variants. PGC-1α promoters are selectively active in distinct tissues in response to specific stimuli. To date, more than ten novel PGC-1α isoforms have been reported to be expressed from a novel promoter (PGC-1α-b, PGC-1α-c), to undergo alternative splicing (NT-PGC-1α) or both (PGC-1α2, PGC-1α3, PGC-1α4). The resulting proteins display differential regulation and tissue distribution and, most importantly, exert specific biological functions. In this review we discuss the structural and functional characteristics of the novel PGC-1α isoforms, aiming to provide an integrative view of this constantly expanding system of transcriptional coactivators.

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Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis

Cited by 1,021 publications

References 64 publications

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

The stem cell factor/Kit signalling pathway regulates mitochondrial function and energy expenditure

The hitchhiker’s guide to PGC-1α isoform structure and biological functions

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