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A dual role for autophagy in a murine model of lung cancer
Autophagy prolongs the survival of cells in stressful conditions but its role in cancer is unclear. Here, Rao et al. show that loss of the autophagic protein Atg5 enhanced cancer incidence but impaired tumour progression in a mouse model of lung cancer.
- Shuan Rao
- , Luigi Tortola
- & Josef M. Penninger
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UTX coordinates steroid hormone-mediated autophagy and cell death
Cells in Drosophila salivary glands undergo hormone-dependent apoptosis when larvae pupate. Here, the authors show that the histone methylase dUTX regulates activation of key cell death and autophagy genes leading to the removal of salivary glands during the Drosophilalarval–pupal transition.
- Donna Denton
- , May T. Aung-Htut
- & Sharad Kumar
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Involvement of mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy
The extent to which damaged and undamaged structures can be segregated within the mitochondrial network during mitophagy is unclear. Abeliovich et al. show that mitochondrial matrix proteins undergo mitophagic degradation at different rates, and that this depends on regulators of mitochondrial dynamics.
- Hagai Abeliovich
- , Mostafa Zarei
- & Joern Dengjel
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| Open AccessAutophagy proteins regulate ERK phosphorylation
The spatial organisation of mitogen-activated protein kinase (MAPK) signalling by scaffold proteins is an important determinant of signalling specificity. Martinez-Lopez et al. show that pre-autophagosomal structures can also act as scaffolds, recruiting the MAPK ERK1/2 and regulating its phosphorylation.
- Nuria Martinez-Lopez
- , Diana Athonvarangkul
- & Rajat Singh
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| Open AccessBase excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy
The chemotherapeutic drug 5-fluorouracil causes cell toxicity by inducing DNA lesions. Here, SenGupta et al. use C. elegansto show that components of the base excision repair and the mismatch repair pathways function together in the response to 5-fluorouracil, resulting in activation of the DNA damage checkpoint and induction of autophagy.
- Tanima SenGupta
- , Maria Lyngaas Torgersen
- & Hilde Nilsen
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Miz1 is required to maintain autophagic flux
Miz1 is a binding partner of the transcription factor c-Myc and a regulator of cell cycle progression. Wolf et al. show that inactivation of Miz1 in the mouse central nervous system results in neurodegeneration, and find that Miz1 is essential for the transcriptional regulation of autophagic flux.
- Elmar Wolf
- , Anneli Gebhardt
- & Martin Eilers
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Bit-by-bit autophagic removal of parkin-labelled mitochondria
Dysfunctional mitochondria are degraded by mitophagy, but how large mitochondria are packed into small autophagic vesicles is unclear. Here the authors show that dysfunctional mitochondria are degraded in a bit-by-bit fashion initiated at sites where parkin-labelled mitochondrial tubules and the endoplasmic reticulum intersect.
- Jin-Yi Yang
- & Wei Yuan Yang
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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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The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans
The mammalian protein TFEB is a key regulator of autophagy, a cellular process implicated in organismal ageing. Here, Lapierre et al. show that the TFEB orthologue HLH-30 is required for lifespan extension in six different long-lived Caenorhabditis elegansstrains.
- Louis R. Lapierre
- , C. Daniel De Magalhaes Filho
- & Malene Hansen
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Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart
Damaged mitochondria are removed from cells through a process called mitophagy. Here, Hoshino et al. show that the cytosolic fraction of the protein p53 inhibits mitophagy by sequestering the mitophagy regulator Parkin, leading to impaired mitochondrial integrity and cardiac function in aged or damaged mouse hearts.
- Atsushi Hoshino
- , Yuichiro Mita
- & Satoaki Matoba
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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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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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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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Selective escape of proteins from the mitochondria during mitophagy
Damaged mitochondria are eliminated from the cell by a form of autophagy called mitophagy. Here the authors show that during mitophagy, specific proteins are rescued from degradation by evacuation from the mitochondria to the endoplasmic reticulum.
- Shotaro Saita
- , Michiko Shirane
- & Keiichi I. Nakayama
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Molecular determinants of selective clearance of protein inclusions by autophagy
Dysfunctional or aggregated proteins in cells are degraded by autophagy. Wong et al.study aggregates of the protein synphilin-1 and show that ubiquitination alters their dynamic properties, which determines whether the aggregates are degraded via basal or inducible forms of autophagy.
- Esther Wong
- , Eloy Bejarano
- & Ana Maria Cuervo
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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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| Open AccessThe miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.
- Ahmet Ucar
- , Shashi K. Gupta
- & Thomas Thum
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Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos
Nutrients and growth factors initiate endocytotic processes in the embryonic endoderm that control embryonic patterning. Here, Kawamuraet al.show that the small GTP-binding protein rab7 controls a unique microautophagy-like process that is involved in endocytosis in the endoderm of mouse embryos.
- Nobuyuki Kawamura
- , Ge-Hong Sun-Wada
- & Yoh Wada
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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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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