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| Open AccessATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy
The protein ATG5 is known to be involved in the formation of autophagosomes. Here, Maskey et al. identify a new role of ATG5 in response to drug-induced DNA damage whereby ATG5 translocates to the nucleus, leading to chromosome misalignment and mitotic catastrophe.
- Dipak Maskey
- , Shida Yousefi
- & Hans-Uwe Simon
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| Open AccessOverexpression of Atg5 in mice activates autophagy and extends lifespan
Changes in autophagy have been shown to modulate lifespan in lower organisms. Here, Pyo et al.show that mice globally overexpressing the autophagy protein Atg5 live longer and are leaner than normal mice, providing the first evidence that increased autophagy extends lifespan in mammals.
- Jong-Ok Pyo
- , Seung-Min Yoo
- & Yong-Keun Jung
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Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress
The kinase ROCK1 has been implicated in apoptosis and other cellular functions. Here Gurkar et al. show that ROCK1 phosphorylates the autophagy regulator Beclin1, which activates autophagy by disrupting the association between Beclin-1 and Bcl-2.
- Aditi U. Gurkar
- , Kiki Chu
- & Sam W. Lee
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Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage
Proteases of the caspase family are important regulators of apoptosis. Here, Zhang et al. present a genetically encoded protein biosensor that fluoresces if cleaved by caspase-3-like proteases, allowing real-time measurements of apoptosis in cells.
- Jiao Zhang
- , Xin Wang
- & Binghui Li
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Spatiotemporally controlled induction of autophagy-mediated lysosome turnover
Lysosomes are the major degradative compartments within cells, but little is known about cellular mechanisms that control lysosome quality. Here Hung et al.show that lysosomes damaged by light-induced activation of a photosensitizer are selectively ubiquitinated and subsequently eliminated by autophagy.
- Yu-Hsien Hung
- , Lily Man-Wen Chen
- & Wei Yuan Yang
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Distinct pathways mediate axon degeneration during apoptosis and axon-specific pruning
Recent studies suggest that there is an overlap between neuronal apoptosis and axon-specific degeneration. Cusack and colleagues show that the caspase-dependent pathways mediating axon degeneration during apoptosis are distinct from those mediating localized axon pruning.
- Corey L. Cusack
- , Vijay Swahari
- & Mohanish Deshmukh
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Article
| Open AccessMutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals
Before antigen exposure, T cell survival is dependent on signalling stimulated by IL-7. Koenen et al. show that upon encountering specific antigen, T cell receptor signalling initiates a different set of survival pathways, which actively suppress those that sustain naive T cells.
- Paul Koenen
- , Susanne Heinzel
- & Philip D. Hodgkin
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Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8
When Salmonella invades human cells, galectin-8 binds host glycans exposed on damaged vesicles and recruits NDP52 to trigger autophagy of the invading microbe. Kim et al. reveal the structure of the NDP52–galectin-8 complex and the basis for its carbohydrate specificity.
- Byeong-Won Kim
- , Seung Beom Hong
- & Hyun Kyu Song
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FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress
DNA replication stress promotes genome instability and cell death. Here Fugger et al.describe how FBH1, via its helicase activity, is required to eliminate cells with excessive DNA replication stress, through the generation of MUS81-induced DNA double-strand breaks.
- Kasper Fugger
- , Wai Kit Chu
- & Claus Storgaard Sørensen
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| Open AccessThe Hedgehog signalling pathway regulates autophagy
Autophagy is a cellular process that controls protein and organelle turnover. Jimenez-Sanchez and colleagues demonstrate in cultured mammalian cells and in fruit fly larvae that autophagy is regulated by Hedgehoc signalling, a pathway that is important for early embryonic development.
- Maria Jimenez-Sanchez
- , Fiona M. Menzies
- & David C. Rubinsztein
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FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
The protein ataxia-telangiectasia mutated (ATM) detects DNA damage and can trigger cellular apoptosis, but how this process is regulated at the molecular level is unclear. Here, Chunget al. show that the transcription factor FOXO3 controls the formation of ATM-containing signalling complexes at sites of DNA damage that trigger apoptosis.
- Young Min Chung
- , See-Hyoung Park
- & Mickey C.-T. Hu
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Ubiquitination and degradation of the FADD adaptor protein regulate death receptor-mediated apoptosis and necroptosis
Fas-associated protein with death domain (FADD) is part of a signalling complex that controls some forms of programmed cell death. Lee and colleagues demonstrate that FADD ubiquitination by the E3 ubiquitin ligase MKRN1 regulates FADD protein stability and thereby cell death.
- Eun-Woo Lee
- , Jung-Hoon Kim
- & Jaewhan Song
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Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression
Tumour cells are subject to replication stress but how cells overcome damage without inducing senescence and apoptotic pathways is unclear. Here, the authors study polyploidy in cancer cells and show that this blocks apoptotic and senescent pathways, resulting in the induction of proteins involved in DNA repair.
- Li Zheng
- , Huifang Dai
- & Binghui Shen
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miR-484 regulates mitochondrial network through targeting Fis1
Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.
- Kun Wang
- , Bo Long
- & Pei-Feng Li
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A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death
Radiomitigating compounds could be used to protect against ionizing radiation. In this study, mitochondria-targeted oleic and stearic acid derivatives are shown to inhibit pro-apoptotic oxidative events, prevent cell death, and protect mice against lethal doses of radiation.
- Jeffrey Atkinson
- , Alexandr A. Kapralov
- & Valerian E. Kagan
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A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
Soluble cytosolic proteins can be degraded in lysosomes by chaperone-mediated autophagy, however, the current method to measure this process requires isolation of lysosomes. Now, a fluorescent reporter is described that can measure this type of autophagy in intact cells.
- Hiroshi Koga
- , Marta Martinez-Vicente
- & Ana Maria Cuervo
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| Open AccessSynthetic human cell fate regulation by protein-driven RNA switches
The control of cell fate and apoptosis is a continuing challenge in synthetic biology. In this study, systems are developed in which an intracellularly expressed genome-encoded protein simultaneously achieves up- and downregulation of two distinct apoptosis pathways.
- Hirohide Saito
- , Yoshihiko Fujita
- & Tan Inoue
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The phospholipase D1 pathway modulates macroautophagy
Macroautophagy involves remodelling of intracellular membranes, but the role of lipids and lipid enzymes in this process is poorly understood. Here, the authors demonstrate that phospholipase D1, an enzyme that catalyses the production of phosphatidic acid, has a modulatory role in the autophagy process in mammalian cells.
- Claudia Dall'Armi
- , Andrés Hurtado-Lorenzo
- & Gilbert Di Paolo