Mitochondrial retrograde signaling in mammals is mediated by the transcriptional cofactor GPS2 via direct mitochondria-to-nucleus translocation
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PROVIDER: PRJNA320244 | ENA |
REPOSITORIES: ENA
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Project description:As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an unexpected layer of regulation of mitochondrial gene transcription, uncover a novel direct mitochondria-nuclear communication pathway and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.
2018-03-21 | GSE80994 | GEO
Project description:As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an unexpected layer of regulation of mitochondrial gene transcription, uncover a novel direct mitochondria-nuclear communication pathway and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.
2018-03-21 | GSE80993 | GEO
Project description:As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an unexpected layer of regulation of mitochondrial gene transcription, uncover a novel direct mitochondria-nuclear communication pathway and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.
2018-03-21 | GSE80992 | GEO
Project description:As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an unexpected layer of regulation of mitochondrial gene transcription, uncover a novel direct mitochondria-nuclear communication pathway and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.
2018-03-21 | GSE80990 | GEO
Project description:As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways in mammals are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a transcriptional activator of nuclear-encoded mitochondrial genes. GPS2-regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of a nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and brown adipose tissue (BAT) from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA POL2 activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an additional layer of regulation of mitochondrial gene transcription, uncover a direct mitochondria-nuclear communication pathway, and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.
| S-EPMC6022402 | biostudies-literature
Project description:The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of TNFA-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFA target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis. RNA-sequencing of polyA selected RNA molecules in 293T cells and ChIP-seq of GPS2, TBL1, and NCOR.
2012-03-23 | E-GEOD-35197 | biostudies-arrayexpress
Project description:Retrograde response was widely studied in budding yeast but the main transcription factors that transmit it (RTG1,2 and 3) are not conserved in other organisms, thus it is interesting to study how communication between mitochondria and nucleus evolved in distantly related fission yeast, and which are the common aspects of this conserved pathway between yeast and higher organisms.To analyse any retrograde response in fission yeast, we inhibited the electron transport chain activity by antimycin A and studied cellular gene expression changes by microarrays. Cells treated with antimycin A in fermentative medium (YE with 3% glucose), showed the same growth rate as untreated cells, but they reached a lower biomass in stationary phase. Antimycin A treated cells consumed glucose at a faster rate and produced more ethanol, indicating that the energy metabolism was shifted even more towards fermentation. We analyzed the transcriptomes of antimycin A-treated cells to untreated control cells during early exponential growth phase (OD 0.5).
2016-11-01 | E-MTAB-4520 | biostudies-arrayexpress
Project description:The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of TNFA-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFA target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis.
2012-03-23 | GSE35197 | GEO
Project description:Strigolactones (SL) are a new class of plant hormones with a broad range of roles in symbiosis, germination and developmental regulation. The well-characterized signaling pathway for SL involves the canonical signaling component MAX2. Here we identified a novel, MAX2-independent SL signaling mechanism, which initiates in mitochondria, signals to the nucleus and regulates root development. By a forward genetic approach, we identified the SL-insensitive pig1 mutant, which altered the kinetic properties of the mitochondrial pyruvate dehydrogenase complex. SL has an unknown target in mitochondria, where it uncouples respiration. This leads to metabolic aberrations, mitochondria-to-nucleus retrograde signaling upregulating transcription of mitochondrial dysfunction genes and downregulating auxin-regulated genes. SL-triggered mitochondrial uncoupling is communicated to the nucleus via cleavage and translocation of the ER-localized transcription factor ANAC017. These observations establish a novel mechanism for SL signaling emanating from mitochondria and regulating development.
2022-04-18 | GSE200634 | GEO
Project description:Strigolactone action in mitochondria triggers retrograde signaling for root growth modulation
| PRJNA825573 | ENA