Abstract:
:Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.
journal_name
Cell Repjournal_title
Cell reportsauthors
Belenky P,Camacho D,Collins JJdoi
10.1016/j.celrep.2012.12.021subject
Has Abstractpub_date
2013-02-21 00:00:00pages
350-8issue
2issn
2211-1247pii
S2211-1247(13)00050-8journal_volume
3pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Here, we ask how neural stem cells (NSCs) transition in the developing neocortex from a rapidly to a slowly proliferating state, a process required to maintain lifelong stem cell pools. We identify LRIG1, known to regulate receptor tyrosine kinase signaling in other cell types, as a negative regulator of cortical NSC ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108257
更新日期:2020-10-13 00:00:00
abstract::Lipoprotein cholesterol is delivered to the limiting membrane of late endosomes/lysosomes (LELs) by Niemann-Pick C1 (NPC1). However, the mechanism of cholesterol transport from LELs to the endoplasmic reticulum (ER) is poorly characterized. We report that oxysterol-binding protein-related protein 1L (ORP1L) is necessa...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.05.028
更新日期:2017-05-30 00:00:00
abstract::T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell developme...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.01.015
更新日期:2016-02-16 00:00:00
abstract::Immunoglobulin M (IgM) memory cells undergo differentiation in germinal centers following antigen challenge, but the full effector cell potential of these cells is unknown. We monitored the differentiation of enhanced yellow fluorescent protein (eYFP)-labeled CD11c+ and CD11cneg T-bet+ IgM memory cells after their tra...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.074
更新日期:2018-07-24 00:00:00
abstract::The mechanisms dictating whether a cell proliferates or differentiates have undergone intense scrutiny, but they remain poorly understood. Here, we report that UPF1, a central component in the nonsense-mediated RNA decay (NMD) pathway, plays a key role in this decision by promoting the proliferative, undifferentiated ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.01.028
更新日期:2014-02-27 00:00:00
abstract::The health of neurons is critically dependent on the relative signaling intensities of survival-promoting synaptic and death-inducing extrasynaptic NMDA receptors. Here, we show that BDNF is a regulator of this balance and promotes neuroprotection by reducing toxic NMDA receptor signaling. BDNF acts by initiating syna...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.07.038
更新日期:2015-08-25 00:00:00
abstract::The thalamus plays a central role in sleep rhythms in the mammalian brain and, yet, surprisingly little is known about its function and interaction with local cortical oscillations during NREM sleep (NREM). We investigated the neuronal correlates of cortical barrel activity in the two corresponding thalamic nuclei, th...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.01.038
更新日期:2019-02-05 00:00:00
abstract::The transcription factor NKX2-1 is best known for its role in the specification of subsets of cortical, striatal, and pallidal neurons. We demonstrate through genetic fate mapping and intersectional focal septal deletion that NKX2-1 is selectively required in the embryonic septal neuroepithelium for the development of...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.07.053
更新日期:2017-08-15 00:00:00
abstract::The root stem cell niche, which is composed of four mitotically inactive quiescent center (QC) cells and the surrounding actively divided stem cells in Arabidopsis, is critical for growth and root development. Here, we demonstrate that the Arabidopsis prohibitin protein PHB3 is required for the maintenance of root ste...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.105
更新日期:2018-01-30 00:00:00
abstract::Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiqu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.05.078
更新日期:2017-06-20 00:00:00
abstract::In humans, Vγ9Vδ2 T cells respond to self and pathogen-associated, diphosphate-containing isoprenoids, also known as phosphoantigens (pAgs). However, activation and homeostasis of Vγ9Vδ2 T cells remain incompletely understood. Here, we show that pAgs induced expression of the ecto-ATPase CD39, which, however, not only...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.009
更新日期:2016-07-12 00:00:00
abstract::Embryonic stem cells (ESCs) hold promise for the treatment of many medical conditions; however, their utility is limited by immune rejection. The objective of our study is to establish tolerance or promote engraftment of transplanted ESCs as well as mature cell populations derived from ESCs. Luciferase (luc(+))-expres...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.02.050
更新日期:2015-03-24 00:00:00
abstract::Medulloblastoma (MB) is a neoplasm linked to dysregulated cerebellar development. Previously, we demonstrated that the Sonic Hedgehog (SHH) subgroup grows hierarchically, with Sox2+ cells at the apex of tumor progression and relapse. To test whether this mechanism is rooted in a normal developmental process, we studie...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.03.075
更新日期:2020-04-14 00:00:00
abstract::Working memory is mediated by the coordinated activation of frontal and parietal cortices occurring in the theta and alpha frequency ranges. Here, we test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory. We identify working memory ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.072
更新日期:2019-11-26 00:00:00
abstract::Changes in epigenetic states affect organismal homeostasis, including stress resistance. However, the mechanisms coordinating epigenetic states and systemic stress resistance remain largely unknown. Here, we identify the intestine-to-germline communication of epigenetic states, which intergenerationally enhances stres...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.050
更新日期:2020-03-10 00:00:00
abstract::The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a cri...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.127
更新日期:2018-05-01 00:00:00
abstract::Many autoimmune and infectious diseases are characterized by the formation of granulomas which are inflammatory lesions that consist of spatially organized immune cells. These sites protect the host and control pathogens like Mycobacterium tuberculosis (Mtb), but are highly inflammatory and cause pathology. Using baci...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.072
更新日期:2019-05-14 00:00:00
abstract::The innate immune system senses cytosolic dsDNA and bacterial cyclic dinucleotides and initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response. We demonstrate here that BTK-deficient cells have impaired IFN-β production and TBK1/IRF3 activation when stimulated with agonists or infected wit...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.01.039
更新日期:2015-02-24 00:00:00
abstract::During chronic infection, the inflammatory cytokine interferon gamma (IFNγ) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, the mechanism by which IFNγ hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we fin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108530
更新日期:2020-12-22 00:00:00
abstract::Parsing diverse nerve cells into biological types is necessary for understanding neural circuit organization. Morphology is an intuitive criterion for neuronal classification and a proxy of connectivity, but morphological diversity and variability often preclude resolving the granularity of neuron types. Combining gen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.040
更新日期:2019-03-12 00:00:00
abstract::Cytotoxic CD8(+) T lymphocytes play a critical role in the host response to infection by viruses. The ability to secrete cytotoxic chemicals and cytokines is considered pivotal for eliminating virus. Of equal importance is how effector CD8(+) T cells home to virus-infected tissues. L-selectin has not been considered i...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.090
更新日期:2016-02-02 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Aβ) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Aβ pathology in vivo, we cr...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.08.042
更新日期:2013-10-17 00:00:00
abstract::The interaction between oxysterols and the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2) fine-tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (MS), such as natalizumab. We previously showed that memory CD4...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.12.006
更新日期:2017-01-03 00:00:00
abstract::Allergic asthma is a highly prevalent airway disease triggered by hyperresponsiveness to inhaled allergens. Interferon regulatory factor 7 (IRF7) has been shown to be highly expressed in nasal aspirates from children with asthma. Type 2 innate lymphoid cells (ILC2s) represent the major player in allergic airway inflam...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.077
更新日期:2019-11-26 00:00:00
abstract::FAM46C is a non-canonical poly(A) polymerase uniquely mutated in up to 20% of multiple myeloma (MM) patients, implying a tissue-specific tumor suppressor function. Here, we report that FAM46C selectively stabilizes mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, thereby concertedly enhancing the expressio...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108162
更新日期:2020-09-22 00:00:00
abstract::Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2011.12.002
更新日期:2012-02-23 00:00:00
abstract::Stable unannotated transcripts (SUTs), some of which overlap protein-coding genes in antisense direction, are a class of non-coding RNAs. While case studies have reported important regulatory roles for several of such RNAs, their general impact on protein abundance regulation of the overlapping gene is not known. To t...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.05.043
更新日期:2016-06-21 00:00:00
abstract::Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.01.045
更新日期:2014-03-13 00:00:00
abstract::Successful anti-viral response requires the sustained activation and expansion of CD8+ T cells for periods that far exceed the time limit of physical T cell interaction with antigen-presenting cells (APCs). The expanding CD8+ T cell pool generates the effector and memory cell populations that provide viral clearance a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.075
更新日期:2018-07-31 00:00:00
abstract::Hepatocyte nuclear factor 4α (HNF4α) is a dimeric transcription factor that controls as much as 60% of all liver genes. However, how it achieves such broad functional diversity is unknown. Here, we show that inflammation and immune pathway genes are differentially regulated in an isoform-dependent manner, confirming t...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.033
更新日期:2019-03-05 00:00:00