Opposing action of NCoR1 and PGC-1α in mitochondrial redox homeostasis

Lima, Tanes I.; Guimarães, Dimitrius Santiago Passos Simões Fróes; Oliveira, André G.; Araújo, Hygor N.; Sponton, Carlos Henrique; Souza-Pinto, Nadja C.; Saito, Ângela; Figueira, Ana Carolina Migliorini; Palameta, Soledad; Bajgelman, Marcio C.; Calixto, Andrea; Pinto, Silas; Mori, Marcelo A.; Orofino, Joey; Perissi, Valentina; Mottis, Adrienne; Auwerx, Johan; Silveira, Leonardo R.

doi:10.1016/j.freeradbiomed.2019.08.006

Cited by 10 publications

(5 citation statements)

References 18 publications

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“…It was one of the most recurrently mutated melanoma genes and was associated with chemoresistance and poor outcome in glioblastoma [50,51]. Importantly, in association with LRP1B mutation, higher TMB and improved outcomes in patients treated by immune checkpoint inhibitors across different cancer types have been described [52,53]. Also, concomitant mutations of KRAS and LRP1B were associated with worse disease-free survival in pancreatic ductal adenocarcinoma [54].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its role in cell cycle regulation, NCOR1 was identified as a central transcriptional repressor check point of genes involved in inflammation [58]. NCOR1 was also involved in regulation of mitochondrial function and ROS generation [52] and required to maintain systemic metabolic homeostasis in vivo [59]. Its alteration has also been associated with enhanced tumor immunogenicity and higher TMB in patients with bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers

Bim

Carneiro

Buzatto

et al. 2021

Cancers

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Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20–30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (ECD, NUP98,LRP1B, NCOR1, ATM, SOS1, and SPOP) and fusions were described. NCOR1 and SPOP variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, RAS, or PAX8-PPARg positive samples. Negative samples were separated in two clusters, following the expression pattern of the RAS/PAX8-PPARg or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers

Bim

Carneiro

Buzatto

et al. 2021

Cancers

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“…The upper and lower rows of Table 2 summarize the names and functions of hypomethylated and hypermethylated genes in granulosa cells of PCOS patients, respectively. The promoter regions of several genes related to glucose metabolism (ANGPTL4 73,74 ), glycolysis (GSTA1 74,75 and SLC12A8 75 ), OXPHOS (SPP1), 76 mitochondrial function (PPARG1, 77 NCOR1, 78 and HDAC3 79 ), apoptosis (NR4A1, 80 PTX3, 81 LIF, 82 BNIP3, 83 and XIAP 84 ), autophagy (PEX3, 85 CYP17A1, 86 and DIRAS3 75 ), and mitophagy (MAPK14 87 ) have been reported to be hypomethylated 75 or hypermethylated 84,88 . See Table 2 for the official full name of each gene symbol.…”

Section: Pathophysiology Of Pcosmentioning

confidence: 99%

Role of the mitophagy‐apoptosis axis in the pathogenesis of polycystic ovarian syndrome

Kobayashi,

Shigetomi,

Matsubara

et al. 2024

J of Obstet and Gynaecol

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AimPolycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by menstrual irregularities, androgen excess, and polycystic ovarian morphology, but its pathogenesis remains largely unknown. This review focuses on how androgen excess influences the molecular basis of energy metabolism, mitochondrial function, and mitophagy in granulosa cells and oocytes, summarizes our current understanding of the pathogenesis of PCOS, and discuss perspectives on future research directions.MethodsA search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review.ResultsFemale offspring born of pregnant animals exposed to androgens recapitulates the PCOS phenotype. Abnormal mitochondrial morphology, altered expression of genes related to glycolysis, mitochondrial biogenesis, fission/fusion dynamics, and mitophagy have been identified in PCOS patients and androgenic animal models. Androgen excess causes uncoupling of the electron transport chain and depletion of the cellular adenosine 5′‐triphosphate pool, indicating further impairment of mitochondrial function. A shift toward mitochondrial fission restores mitochondrial quality control mechanisms. However, prolonged mitochondrial fission disrupts autophagy/mitophagy induction due to loss of compensatory reserve for mitochondrial biogenesis. Disruption of compensatory mechanisms that mediate the quality control switch from mitophagy to apoptosis may cause a disease phenotype. Furthermore, genetic predisposition, altered expression of genes related to glycolysis and oxidative phosphorylation, or a combination of these factors may also contribute to the development of PCOS.ConclusionIn conclusion, fetuses exposed to a hyperandrogenemic intrauterine environment may cause the PCOS phenotype possibly through disruption of the compensatory regulation of the mitophagy‐apoptosis axis.

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“…We recently provided evidence that the transcriptional regulation of UCP3 by the peroxisome proliferator-activated receptor γ co-receptor 1-α (PGC-1α) is essential for the maintenance of myotube viability during lipid overload, by preventing the production of reactive oxygen species (ROS) (Lima et al , 2019. Considering a similar phenotype by Nr2f6 knockdown in myotubes, we investigated whether Nr2f6 regulates the same pathway.…”

Section: Nr2f6 Regulates Pgc-1α and Ucp3 Expressionmentioning

confidence: 99%

Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6

Guimarães,

Barrios,

de Oliveira

et al. 2023

Preprint

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The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and activity depends on the crosstalk between metabolic and structural adaptations. Here, we establish a role for the orphan nuclear receptor Nr2f6 in both processes. Nr2f6 overexpression leads to an atrophic state, sharply decreasing muscle mass and myofiber content, which is accompanied by an impairment in force production. These functional phenotypes were followed by the establishment of an inflammatory molecular signature, and a decrease in genes involved in oxidative metabolism and contractility. Conversely, Nr2f6 depletion increased myocytes' oxidative capacity and protected against lipid-induced cell death. In addition, Nr2f6 regulated core components of the cell division machinery, decoupling muscle cell proliferation from differentiation. Collectively, our findings define a novel role for Nr2f6 as a molecular transducer conferring the balance between skeletal muscle structure and oxidative capacity.

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Opposing action of NCoR1 and PGC-1α in mitochondrial redox homeostasis

Cited by 10 publications

References 18 publications

Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers

Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers

Role of the mitophagy‐apoptosis axis in the pathogenesis of polycystic ovarian syndrome

Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6

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