cAMP-induced Mitochondrial Compartment Biogenesis

Yoboue, Edgar D.; Augier, Eric; Galinier, Anne; Blancard, Corinne; Pinson, Benoı̂t; Casteilla, Louis; Rigoulet, Michel; Devin, Anne

doi:10.1074/jbc.m111.302786

Cited by 21 publications

(17 citation statements)

References 48 publications

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“…In the yeast Saccharomyces cerevisiae, the transcription factors Hap2p/3p/4p/5p -HAP complex-are the master regulators of mitochondrial biogenesis (7,8). This heteromeric complex relies on the binding to the promoter of target genes by recently demonstrated that PGC-1α is regulated by the glutathione redox state, as we previously showed for Hap4p (16,17). Previous studies also established the involvement of reactive oxygen species (ROS) and cAMP-dependent signaling in negative and positive regulation of the transcriptional regulators of mitochondrial biogenesis in both yeast and mammals (5,(18)(19)(20)(21).…”

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confidence: 86%

“Labile” heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in Saccharomyces cerevisiae

Bouchez

Yoboue

Vargas

et al. 2020

Journal of Biological Chemistry

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Heme (iron protoporphyrin IX) is a well-known prosthetic group for enzymes involved in metabolic pathways such as oxygen transport and electron transfer through the mitochondrial respiratory chain. However, heme has also been shown to be an important regulatory molecule (as “labile” heme) for diverse processes such as translation, kinase activity, and transcription in mammals, yeast, and bacteria. Taking advantage of a yeast strain deficient for heme production that enabled controlled modulation and monitoring of labile heme levels, here we investigated the role of labile heme in the regulation of mitochondrial biogenesis. This process is regulated by the HAP complex in yeast. Using several biochemical assays along with EM and epifluorescence microscopy, to the best of our knowledge, we show for the first time that cellular labile heme is critical for the post-translational regulation of HAP complex activity, most likely through the stability of the transcriptional co-activator Hap4p. Consequently, we found that labile heme regulates mitochondrial biogenesis and cell growth. The findings of our work highlight a new mechanism in the regulation of mitochondrial biogenesis by cellular metabolites.

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confidence: 86%

“Labile” heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in Saccharomyces cerevisiae

Bouchez

Yoboue

Vargas

et al. 2020

Journal of Biological Chemistry

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“…Previous work from our laboratory has shown a tight link between the activity of this signaling pathway and the cellular content in mitochondria [24,32,33,34,35]. It should be stressed here that throughout this review, mitochondrial content will refer to the cellular amount of mitochondrial cytochromes, a robust parameter that allows cellular quantitation of mitochondrial respiratory chain amount [36].…”

Section: Ros-induced Downregulation Of Mitochondrial Biogenesis Inmentioning

confidence: 99%

“…Exogenous cAMP addition to this strain increases HAP complex activity and thus mitochondrial biogenesis. cAMP triggers an enhancement of Hap4p stability, the regulator of the HAP complex [32]. Consequently, an increase in the cAMP pathway activity positively regulates mitochondrial biogenesis.…”

Section: Ros-induced Downregulation Of Mitochondrial Biogenesis Inmentioning

confidence: 99%

“…Even though this mutant is sensitive to oxidative stress [49], it is perfectly viable and the glutathione redox state can be increased in the mutant by addition of exogenous reduced glutathione to the culture medium [50]. We were able to show that the amount of transcription co-activator Hap4p (and consequently mitochondrial biogenesis) was decreased in the Δglr1 strain and its amount increased back when reduced glutathione was added to the culture medium, whereas ascorbate and lipoate had no effect on Hap4p amount either in the wild type cells or in the Δglr1 cells [32]. This supports a specific role of the glutathione redox state in the control of the biogenesis of the mitochondrial compartment through Hap4p.…”

Section: Ros-induced Downregulation Of Mitochondrial Biogenesis Inmentioning

confidence: 99%

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Mitochondrial Biogenesis and Mitochondrial Reactive Oxygen Species (ROS): A Complex Relationship Regulated by the cAMP/PKA Signaling Pathway

Bouchez

Devin

2019

Cells

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168

100

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Mitochondrial biogenesis is a complex process. It requires the contribution of both the nuclear and the mitochondrial genomes and therefore cross talk between the nucleus and mitochondria. Cellular energy demand can vary by great length and it is now well known that one way to adjust adenosine triphosphate (ATP) synthesis to energy demand is through modulation of mitochondrial content in eukaryotes. The knowledge of actors and signals regulating mitochondrial biogenesis is thus of high importance. Here, we review the regulation of mitochondrial biogenesis both in yeast and in mammalian cells through mitochondrial reactive oxygen species.

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“…of the most important modulator of mitochondrial biogenesis in yeast, that is, the transcriptional coactivator Hap4p (49). It is likely that a reducing environment is fundamental for the function of PGC-1a as a coactivator of mitochondrial genes.…”

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confidence: 99%

p53 Orchestrates the PGC-1α-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance

Aquilano

Baldelli²,

Pagliei

et al. 2013

Antioxidants & Redox Signaling

177

183

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Aims: The transcriptional coactivator peroxisome proliferator-activated receptor-c coactivator-1 a (PPARGC1A or PGC-1a) is a powerful controller of cell metabolism and assures the balance between the production and the scavenging of pro-oxidant molecules by coordinating mitochondrial biogenesis and the expression of antioxidants. However, even though a huge amount of data referring to the role of PGC-1a is available, the molecular mechanisms of its regulation at the transcriptional level are not completely understood. In the present report, we aim at characterizing whether the decrease of antioxidant glutathione (GSH) modulates PGC-1a expression and its downstream metabolic pathways. Results: We found that upon GSH shortage, induced either by its chemical depletion or by metabolic stress (i.e., fasting), p53 binds to the PPARGC1A promoter of both human and mouse genes, and this event is positively related to increased PGC-1a expression. This effect was abrogated by inhibiting nitric oxide (NO) synthase or guanylate cyclase, implicating NO/cGMP signaling in such a process. We show that p53-mediated PGC-1a upregulation is directed to potentiate the antioxidant defense through nuclear factor (erythroid-derived 2)-like2 (NFE2L2)-mediated expression of manganese superoxide dismutase (SOD2) and c-glutamylcysteine ligase without modulating mitochondrial biogenesis. Innovation and Conclusions: We outlined a new NO-dependent signaling axis responsible for survival antioxidant response upon mild metabolic stress (fasting) and/or oxidative imbalance (GSH depletion). Such signaling axis could become the cornerstone for new pharmacological or dietary approaches for improving antioxidant response during ageing and human pathologies associated with oxidative stress. Antioxid. Redox Signal. 18, 386-399.

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cAMP-induced Mitochondrial Compartment Biogenesis

Cited by 21 publications

References 48 publications

“Labile” heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in Saccharomyces cerevisiae

“Labile” heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in Saccharomyces cerevisiae

Mitochondrial Biogenesis and Mitochondrial Reactive Oxygen Species (ROS): A Complex Relationship Regulated by the cAMP/PKA Signaling Pathway

p53 Orchestrates the PGC-1α-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance

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