Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells.

Abstract:

:The tricarboxylic acid (TCA) cycle is the central hub of oxidative metabolism, running in the classic forward direction to provide carbon for biosynthesis and reducing agents for generation of ATP. Our metabolic tracer studies in melanoma cells showed that in hypoxic conditions the TCA cycle is largely disconnected from glycolysis. By studying the TCA branch point metabolites, acetyl CoA and citrate, as well as the metabolic endpoint glutamine and fatty acids, we developed a comprehensive picture of the rewiring of the TCA cycle that occurs in hypoxia. Hypoxic tumor cells maintain proliferation by running the TCA cycle in reverse. The source of carbon for acetyl CoA, citrate, and fatty acids switches from glucose in normoxia to glutamine in hypoxia. This hypoxic flux from glutamine into fatty acids is mediated by reductive carboxylation. This reductive carboxylation is catalyzed by two isocitrate dehydrogenases, IDH1 and IDH2. Their combined action is necessary and sufficient to effect the reverse TCA flux and maintain cellular viability.

authors

Filipp FV,Scott DA,Ronai ZA,Osterman AL,Smith JW

doi

10.1111/j.1755-148X.2012.00989.x

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

375-83

issue

3

eissn

1755-1471

issn

1755-148X

journal_volume

25

pub_type

杂志文章
  • The Dark brown plumage color in chickens is caused by an 8.3-kb deletion upstream of SOX10.

    abstract::The Dark brown (DB) mutation in chickens reduces expression of black eumelanin and enhances expression of red pheomelanin, but only in certain parts of the plumage. Here, we present genetic evidence that an 8.3-kb deletion upstream of the SOX10 transcription start site is the causal mutation underlying the DB phenotyp...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2011.00825.x

    authors: Gunnarsson U,Kerje S,Bed'hom B,Sahlqvist AS,Ekwall O,Tixier-Boichard M,Kämpe O,Andersson L

    更新日期:2011-04-01 00:00:00

  • Loss of Klotho during melanoma progression leads to increased filamin cleavage, increased Wnt5A expression, and enhanced melanoma cell motility.

    abstract::We have previously shown that Wnt5A-mediated signaling can promote melanoma metastasis. It has been shown that Wnt signaling is antagonized by the protein Klotho, which has been implicated in aging. We show here that in melanoma cells, expressions of Wnt5A and Klotho are inversely correlated. In the presence of recomb...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2010.00792.x

    authors: Camilli TC,Xu M,O'Connell MP,Chien B,Frank BP,Subaran S,Indig FE,Morin PJ,Hewitt SM,Weeraratna AT

    更新日期:2011-02-01 00:00:00

  • Postnatal lineage mapping of follicular melanocytes with the Tyr::CreER(T) (2) transgene.

    abstract::One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr::CreER(T) ...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12048

    authors: Harris ML,Pavan WJ

    更新日期:2013-03-01 00:00:00

  • T-type calcium channel blockers inhibit autophagy and promote apoptosis of malignant melanoma cells.

    abstract::We have recently reported that human melanoma cells express a variety of voltage-gated calcium (Ca(2+) ) channel types, including low-voltage-activated T-type channels that play a significant role in melanoma cell cycle progression. Here, we challenged melanoma metastatic cells with T-type channel blockers of clinical...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12155

    authors: Das A,Pushparaj C,Herreros J,Nager M,Vilella R,Portero M,Pamplona R,Matias-Guiu X,Martí RM,Cantí C

    更新日期:2013-11-01 00:00:00

  • Human hair melanins: what we have learned and have not learned from mouse coat color pigmentation.

    abstract::Hair pigmentation is one of the most conspicuous phenotypes in humans. Melanocytes produce two distinct types of melanin pigment: brown to black, indolic eumelanin and yellow to reddish brown, sulfur-containing pheomelanin. Biochemically, the precursor tyrosine and the key enzyme tyrosinase and the tyrosinase-related ...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2010.00755.x

    authors: Ito S,Wakamatsu K

    更新日期:2011-02-01 00:00:00

  • Keratinocytes in culture accumulate phagocytosed melanosomes in the perinuclear area.

    abstract::There are many techniques for evaluating melanosome transfer to keratinocytes but the spectrophotometric quantification of melanosomes incorporated by keratinocyte phagocytosis has not been previously reported. Here we describe a new method that allows the spectrophotometric visualization of melanosome uptake by norma...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2009.00640.x

    authors: Ando H,Niki Y,Yoshida M,Ito M,Akiyama K,Kim JH,Yoon TJ,Lee JH,Matsui MS,Ichihashi M

    更新日期:2010-02-01 00:00:00

  • NGS-based 100-gene panel of hypopigmentation identifies mutations in Chinese Hermansky-Pudlak syndrome patients.

    abstract::Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chine...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12534

    authors: Wei A,Yuan Y,Bai D,Ma J,Hao Z,Zhang Y,Yu J,Zhou Z,Yang L,Yang X,Li L,Li W

    更新日期:2016-11-01 00:00:00

  • The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival.

    abstract::Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12653

    authors: Orlow I,Shi Y,Kanetsky PA,Thomas NE,Luo L,Corrales-Guerrero S,Cust AE,Sacchetto L,Zanetti R,Rosso S,Armstrong BK,Dwyer T,Venn A,Gallagher RP,Gruber SB,Marrett LD,Anton-Culver H,Busam K,Begg CB,Berwick M,GEM Study

    更新日期:2018-03-01 00:00:00

  • Decreased regulatory T-cells and CD4(+) /CD8(+) ratio correlate with disease onset and progression in patients with generalized vitiligo.

    abstract::The aim of present study was to evaluate CD4(+) /CD8(+) ratio and CD4(+) CD25(hi) FoxP3(+) Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4(+) /CD8(+) ratio and Tregs in 82 patients and 50 controls. CD8(+) T-cell counts were signific...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12105

    authors: Dwivedi M,Laddha NC,Arora P,Marfatia YS,Begum R

    更新日期:2013-07-01 00:00:00

  • Re-evaluation of insect melanogenesis research: Views from the dark side.

    abstract::Melanins (eumelanin and pheomelanin) are synthesized in insects for several purposes including cuticle sclerotization and color patterning, clot formation, organogenesis, and innate immunity. Traditional views of insect immunity detail the storage of pro-phenoloxidases inside specialized blood cells (hemocytes) and th...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/pcmr.12590

    authors: Whitten MMA,Coates CJ

    更新日期:2017-07-01 00:00:00

  • The mouse ruby-eye 2(d) (ru2(d) /Hps5(ru2-d) ) allele inhibits eumelanin but not pheomelanin synthesis.

    abstract::The novel mutation named ru2(d) /Hps5(ru2-d) , characterized by light-colored coats and ruby-eyes, prohibits differentiation of melanocytes by inhibiting tyrosinase (Tyr) activity, expression of Tyr, Tyr-related protein 1 (Tyrp1), Tyrp2, and Kit. However, it is not known whether the ru2(d) allele affects pheomelanin s...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12118

    authors: Hirobe T,Ito S,Wakamatsu K

    更新日期:2013-09-01 00:00:00

  • Genomic characterisation of acral melanoma cell lines.

    abstract::Acral melanoma is a rare melanoma subtype with distinct epidemiological, clinical and genetic features. To determine if acral melanoma cell lines are representative of this melanoma subtype, six lines were analysed by whole-exome sequencing and array comparative genomic hybridisation. We demonstrate that the cell line...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2012.01016.x

    authors: Furney SJ,Turajlic S,Fenwick K,Lambros MB,MacKay A,Ricken G,Mitsopoulos C,Kozarewa I,Hakas J,Zvelebil M,Lord CJ,Ashworth A,Reis-Filho JS,Herlyn M,Murata H,Marais R

    更新日期:2012-07-01 00:00:00

  • Vitiligo as an inflammatory skin disorder: a therapeutic perspective.

    abstract::From a therapeutic standpoint, vitiligo is still regarded by many physicians as a simple problem of regenerative medicine, with the main aim to repopulate the depigmented skin with functional melanocytes from the margins of the lesions or from intact progenitors in hair follicles. However, recent research in vitiligo ...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-148X.2011.00939.x

    authors: Taïeb A

    更新日期:2012-01-01 00:00:00

  • Generation of melanocytes from neural crest cells.

    abstract::The neural crest is a transient structure in vertebrate embryos that generates multiple neural and mesenchymal cell types as well as melanocytes. Melanocytes in the skin either derive directly from neural crest cells populating the skin via a dorsolateral migratory pathway or arise by detaching from nerves innervating...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-148X.2011.00834.x

    authors: Sommer L

    更新日期:2011-06-01 00:00:00

  • Independent regulation of hair and skin color by two G protein-coupled pathways.

    abstract::Hair color and skin color are frequently coordinated in mammalian species. To explore this, we have studied mutations in two different G protein coupled pathways, each of which affects the darkness of both hair and skin color. In each mouse mutant (Gnaq(Dsk1), Gna11(Dsk7), and Mc1r(e)), we analyzed the melanocyte dens...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2009.00609.x

    authors: Van Raamsdonk CD,Barsh GS,Wakamatsu K,Ito S

    更新日期:2009-12-01 00:00:00

  • The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin.

    abstract::Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the ...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-148X.2011.00880.x

    authors: Whiteman DC,Pavan WJ,Bastian BC

    更新日期:2011-10-01 00:00:00

  • The state of melanoma: challenges and opportunities.

    abstract::The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - dia...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12475

    authors: Merlino G,Herlyn M,Fisher DE,Bastian BC,Flaherty KT,Davies MA,Wargo JA,Curiel-Lewandrowski C,Weber MJ,Leachman SA,Soengas MS,McMahon M,Harbour JW,Swetter SM,Aplin AE,Atkins MB,Bosenberg MW,Dummer R,Gershenwald JE,Ha

    更新日期:2016-07-01 00:00:00

  • The tumor suppressor BAP1 cooperates with BRAFV600E to promote tumor formation in cutaneous melanoma.

    abstract::The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAFV600E ) and UV to cause melanoma in mice, albeit at very low freque...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12735

    authors: Webster JD,Pham TH,Wu X,Hughes NW,Li Z,Totpal K,Lee HJ,Calses PC,Chaurushiya MS,Stawiski EW,Modrusan Z,Chang MT,Tran C,Lee WP,Chalasani S,Hung J,Sharma N,Chan S,Hotzel K,Talevich E,Shain A,Xu M,Lill J,Dixit

    更新日期:2019-03-01 00:00:00

  • ABCB5 is activated by MITF and β-catenin and is associated with melanoma differentiation.

    abstract::Defining markers of different phenotypic states in melanoma is important for understanding disease progression, determining the response to therapy, and defining the molecular mechanisms underpinning phenotype-switching driven by the changing intratumor microenvironment. The ABCB5 transporter is implicated in drug-res...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12830

    authors: Louphrasitthiphol P,Chauhan J,Goding CR

    更新日期:2020-01-01 00:00:00

  • Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A.

    abstract::The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGF...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12255

    authors: Hwang HW,Baxter LL,Loftus SK,Cronin JC,Trivedi NS,Borate B,Pavan WJ

    更新日期:2014-09-01 00:00:00

  • MicroRNA-125a promotes resistance to BRAF inhibitors through suppression of the intrinsic apoptotic pathway.

    abstract::Melanoma patients with BRAFV600E -mutant tumors display striking responses to BRAF inhibitors (BRAFi); however, almost all invariably relapse with drug-resistant disease. Here, we report that microRNA-125a (miR-125a) expression is upregulated in human melanoma cells and patient tissues upon acquisition of BRAFi resist...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12578

    authors: Koetz-Ploch L,Hanniford D,Dolgalev I,Sokolova E,Zhong J,Díaz-Martínez M,Bernstein E,Darvishian F,Flaherty KT,Chapman PB,Tawbi H,Hernando E

    更新日期:2017-05-01 00:00:00

  • NLRP1, a regulator of innate immunity associated with vitiligo.

    abstract::Some familial forms of the dermatological condition vitiligo have recently been linked to polymorphisms in the innate immunity gene, NLRP1. Here, we review what is currently known about the mechanisms that regulate activation of the NLRP1 protein and the downstream effects of NLRP1 on pathways impacting inflammation a...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-148X.2011.00942.x

    authors: D'Osualdo A,Reed JC

    更新日期:2012-01-01 00:00:00

  • NRASQ61K melanoma tumor formation is reduced by p38-MAPK14 activation in zebrafish models and NRAS-mutated human melanoma cells.

    abstract::Oncogenic BRAF and NRAS mutations drive human melanoma initiation. We used transgenic zebrafish to model NRAS-mutant melanoma, and the rapid tumor onset allowed us to study candidate tumor suppressors. We identified P38α-MAPK14 as a potential tumor suppressor in The Cancer Genome Atlas melanoma cohort of NRAS-mutant m...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12925

    authors: Banik I,Cheng PF,Dooley CM,Travnickova J,Merteroglu M,Dummer R,Patton EE,Busch-Nentwich EM,Levesque MP

    更新日期:2020-09-10 00:00:00

  • LIGR, a protease-activated receptor-2-derived peptide, enhances skin pigmentation without inducing inflammatory processes.

    abstract::The protease-activated receptor-2 (PAR-2) is a seven transmembrane G-protein-coupled receptor that could be activated by serine protease cleavage or by synthetic peptide agonists. We showed earlier that activation of PAR-2 with Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLIGRL), a known PAR-2 activating peptide, induces keratinoc...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2008.00441.x

    authors: Lin CB,Chen N,Scarpa R,Guan F,Babiarz-Magee L,Liebel F,Li WH,Kizoulis M,Shapiro S,Seiberg M

    更新日期:2008-04-01 00:00:00

  • Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation.

    abstract::Mutations within the OCA2 gene or the complete absence of the OCA2 protein leads to oculocutaneous albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated with pig...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/pcmr.12210

    authors: Visser M,Kayser M,Grosveld F,Palstra RJ

    更新日期:2014-03-01 00:00:00

  • Melasma, a photoaging disorder.

    abstract::Melasma is a common hyperpigmentary disorder. The impact on the quality of life of affected individuals is well demonstrated, demanding new therapeutic strategies. However, the treatment of melasma remains highly challenging. Melasma is often considered as the main consequence of female hormone stimulation on a predis...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/pcmr.12684

    authors: Passeron T,Picardo M

    更新日期:2018-07-01 00:00:00

  • NRG1 / ERBB3 signaling in melanocyte development and melanoma: inhibition of differentiation and promotion of proliferation.

    abstract::Neuregulin (NRG) signaling through the receptor tyrosine kinase, ERBB3, is required for embryonic development, and dysregulated signaling has been associated with cancer progression. Here, we show that NRG1/ERBB3 signaling inhibits melanocyte (MC) maturation and promotes undifferentiated, migratory and proliferative c...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/j.1755-148X.2009.00616.x

    authors: Buac K,Xu M,Cronin J,Weeraratna AT,Hewitt SM,Pavan WJ

    更新日期:2009-12-01 00:00:00

  • Premature senescence in human melanocytes after exposure to solar UVR: An exosome and UV-miRNA connection.

    abstract::Ultraviolet radiation (UVR) can play two roles: induce cellular senescence and convert skin melanocytes into melanoma. To assess whether this conversion might rely on melanocytes having to first acquire a senescent phenotype, we studied the effects of physiological doses of UVR (UVA + UVB) on quiescent melanocytes in ...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12888

    authors: Sha J,Arbesman J,Harter ML

    更新日期:2020-09-01 00:00:00

  • Current opportunities and challenges: genome-wide association studies on pigmentation and skin cancer.

    abstract::Genome-wide association studies (GWAS) have become a widely used approach for genetic association studies of various human traits. A few GWAS have been conducted with the goal of identifying novel loci for pigmentation traits, melanoma, and non-melanoma skin cancer. Nevertheless, the phenotype variation explained by t...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-148X.2012.01023.x

    authors: Meng S,Zhang M,Liang L,Han J

    更新日期:2012-09-01 00:00:00

  • Two light-activated neuroendocrine circuits arising in the eye trigger physiological and morphological pigmentation.

    abstract::Two biological processes regulate light-induced skin colour change. A fast 'physiological pigmentation change' (i.e. circadian variations or camouflage) involves alterations in the distribution of pigment containing granules in the cytoplasm of chromatophores, while a slower 'morphological pigmentation change' (i.e. s...

    journal_title:Pigment cell & melanoma research

    pub_type: 杂志文章

    doi:10.1111/pcmr.12531

    authors: Bertolesi GE,Hehr CL,Munn H,McFarlane S

    更新日期:2016-11-01 00:00:00