Abstract:
:Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and previous we have shown that these two effectors are also needed for mitochondrial-dependent cellular necrosis (Karch et al., 2013). Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells. Moreover, a monomeric-only mutant form of Bax is sufficient to increase lysosomal membrane permeability and restore autophagic cell death in Bax/Bak1 double-deleted mouse embryonic fibroblasts. Finally, increasing lysosomal permeability through a lysomotropic detergent in cells devoid of Bax/Bak1 restores autophagic cell death, collectively indicting that Bax/Bak integrate all major forms of cell death through direct effects on membrane permeability of multiple intracellular organelles.
journal_name
Elifejournal_title
eLifeauthors
Karch J,Schips TG,Maliken BD,Brody MJ,Sargent MA,Kanisicak O,Molkentin JDdoi
10.7554/eLife.30543subject
Has Abstractpub_date
2017-11-17 00:00:00issn
2050-084Xpii
30543journal_volume
6pub_type
杂志文章相关文献
eLife文献大全abstract::Multi-modal MRI techniques have identified biomarkers that could help to predict whether someone will develop epilepsy. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.29853
更新日期:2017-07-26 00:00:00
abstract::Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretation of simulations. However, the number of published models, and the lack of standardization, make the comparison of ion channel models with one another and with experimental dat...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22152
更新日期:2017-03-06 00:00:00
abstract::DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.24284
更新日期:2017-04-25 00:00:00
abstract::Despite their importance in sexual differentiation and reproduction, Y chromosome genes are rarely described because they reside in repeat-rich regions that are difficult to study. Here, we show that Guy1, a unique Y chromosome gene of a major urban malaria mosquito Anopheles stephensi, confers 100% female lethality w...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19281
更新日期:2016-09-20 00:00:00
abstract::Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.36998
更新日期:2018-05-10 00:00:00
abstract::Epicardial cells on the heart's surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.10036
更新日期:2015-10-19 00:00:00
abstract::The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34420
更新日期:2018-03-28 00:00:00
abstract::Analysis of the spatial distribution of endomembrane trafficking is fundamental to understand the mechanisms controlling cellular dynamics, cell homeostasy, and cell interaction with its external environment in normal and pathological situations. We present a semi-parametric framework to quantitatively analyze and vis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.32311
更新日期:2018-08-09 00:00:00
abstract::Adipocyte differentiation is a strictly controlled process regulated by a series of transcriptional activators. Adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by late enhanceosomes....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05615
更新日期:2015-04-23 00:00:00
abstract::Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14137
更新日期:2016-05-10 00:00:00
abstract::To move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. Here, we use in vivo calcium imaging, electrophysiology, and behavior to understand how genetically-identified motor neurons control flexion of the fruit fly tibia. We find that leg motor neurons exhi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56754
更新日期:2020-06-03 00:00:00
abstract::Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1, and R2TP. Interesti...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.63042
更新日期:2020-11-18 00:00:00
abstract::Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04402
更新日期:2014-10-06 00:00:00
abstract::Convenient, efficient and fast whole-brain delivery of transgenes presents a persistent experimental challenge in neuroscience. Recent advances demonstrate whole-brain gene delivery by retro-orbital injection of virus, but slow and sparse expression and the large injection volumes required make this approach cumbersom...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53639
更新日期:2020-05-18 00:00:00
abstract::Purkinje neurons are central to cerebellar function and show membrane bistability when recorded in vitro or in vivo under anesthesia. The existence of bistability in vivo in awake animals is disputed. Here, by recording intracellularly from Purkinje neurons in unanesthetized larval zebrafish (Danio rerio), we unequivo...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.09158
更新日期:2015-09-29 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving cytotoxic conformations of Cu, Zn superoxide dismutase (SOD1). A major challenge in understanding ALS disease pathology has been the identification and atomic-level characterization of these conformers. Here, we use a combination ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07296
更新日期:2015-06-23 00:00:00
abstract::Meiotic crossovers result from homology-directed repair of DNA double-strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53360
更新日期:2020-04-30 00:00:00
abstract::Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde tra...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41896
更新日期:2019-06-17 00:00:00
abstract::The mesiotemporal lobe (MTL) is implicated in many cognitive processes, is compromised in numerous brain disorders, and exhibits a gradual cytoarchitectural transition from six-layered parahippocampal isocortex to three-layered hippocampal allocortex. Leveraging an ultra-high-resolution histological reconstruction of ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.60673
更新日期:2020-11-04 00:00:00
abstract::Precise and efficient manipulation of genes is crucial for understanding the molecular mechanisms that govern human hematopoiesis and for developing novel therapies for diseases of the blood and immune system. Current methods do not enable precise engineering of complex genotypes that can be easily tracked in a mixed ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27873
更新日期:2017-09-28 00:00:00
abstract::Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-conta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04664
更新日期:2014-12-02 00:00:00
abstract::Replication-dependent (RD) core histone mRNA produced during S-phase is the only known metazoan protein-coding mRNA presenting a 3' stem-loop instead of the otherwise universal polyA tail. A metallo β-lactamase (MBL) fold enzyme, cleavage and polyadenylation specificity factor 73 (CPSF73), is proposed to be the sole e...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.39865
更新日期:2018-12-03 00:00:00
abstract::Complexin regulates spontaneous and activates Ca(2+)-triggered neurotransmitter release, yet the molecular mechanisms are still unclear. Here we performed single molecule fluorescence resonance energy transfer experiments and uncovered two conformations of complexin-1 bound to the ternary SNARE complex. In the cis con...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.16886
更新日期:2016-06-02 00:00:00
abstract::Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cereb...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48702
更新日期:2019-09-06 00:00:00
abstract::The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene exp...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22906
更新日期:2017-02-22 00:00:00
abstract::The eukaryotic replisome assembles around the CMG helicase, which stably associates with DNA replication forks throughout elongation. When replication terminates, CMG is ubiquitylated on its Mcm7 subunit and disassembled by the Cdc48/p97 ATPase. Until now, the regulation that restricts CMG ubiquitylation to terminatio...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.60371
更新日期:2020-08-17 00:00:00
abstract::An 'interactome' screen of all Drosophila cell-surface and secreted proteins containing immunoglobulin superfamily (IgSF) domains discovered a network formed by paralogs of Beaten Path (Beat) and Sidestep (Side), a ligand-receptor pair that is central to motor axon guidance. Here we describe a new method for interacto...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.28111
更新日期:2017-08-15 00:00:00
abstract::C-type inactivation of potassium channels fine-tunes the electrical signaling in excitable cells through an internal timing mechanism that is mediated by a hydrogen bond network in the channels' selectively filter. Previously, we used nonsense suppression to highlight the role of the conserved Trp434-Asp447 indole hyd...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18976
更新日期:2016-10-06 00:00:00
abstract::Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.17670
更新日期:2016-07-06 00:00:00
abstract::Pathological metabolic conditions such as ischemia induce the rupture of the mitochondrial envelope and the release of pro-apoptotic proteins, leading to cell death. At the onset of this process, the inner mitochondrial membrane becomes depolarized and permeable to osmolytes, proposedly due to the opening of a non-sel...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23781
更新日期:2017-02-10 00:00:00