Lysosomes articles within Nature Communications

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  • Article
    | Open Access

    Though endocytosed dietary cholesterol is transferred to the endoplasmic reticulum (ER), how this is regulated is unclear. Here, the authors report a role for Niemann-Pick Type C Protein 1 (NPC1) in tethering endocytic organelles to the ER, which may contribute to interorganelle cholesterol transport.

    • D. Höglinger
    • , T. Burgoyne
    •  & E. R Eden

  • Article
    | Open Access

    After autophagic cargo degradation, autolysosomes undergo a reformation process to recycle lysosomal membrane components. Here, Dai et al. demonstrate that the actin nucleation promoting factor WHAMM is required for autolysosome reformation by providing an actin scaffold to drive tubulation.

    • Anbang Dai
    • , Li Yu
    •  & Hong-Wei Wang

  • Article
    | Open Access

    Mutations in equilibrative nucleoside transporter 3 (ENT3), encoded by SLC29A3, cause a spectrum of human genetic disorders. Here, the authors show altered haematopoietic stem cell and mesenchymal stem cell fates in ENT3-deficient mice, due to misregulation of the AMPK-mTOR-ULK axis.

    • Sreenath Nair
    • , Anne M. Strohecker
    •  & Rajgopal Govindarajan

  • Article
    | Open Access

    How cells regulate their lysosomal proteolytic capacity is only partly understood. Here, the authors show that lysosomal protease deficiency or substrate overload induces lysosomal stress leading to activation of a STAT3-dependent, TFEB-independent pathway of lysosomal hydrolase expression.

    • Jonathan Martínez-Fábregas
    • , Alan Prescott
    •  & Colin Watts

  • Article
    | Open Access

    Neurodegeneration is increasingly associated with endolysosomal and autophagy dysfunction. Here, Miranda and colleagues show that disruption of neuronal PI3P/Vps34 signaling leads to endolysosomal membrane damage and aberrant release of undigested material in APP-CTF- and BMP-positive exosomes.

    • André M. Miranda
    • , Zofia M. Lasiecka
    •  & Gilbert Di Paolo

  • Article
    | Open Access

    Nephropathic cystinosis is a lysosomal storage disease characterized by proximal tubular cell dysfunction. Here Festa and colleagues show that these lysosomal alterations lead to defective autophagic clearance of mitochondria and increased oxidative stress that, in turn, activates the transcription factor ZONAB leading to impaired cell differentiation.

    • Beatrice Paola Festa
    • , Zhiyong Chen
    •  & Alessandro Luciani

  • Article
    | Open Access

    The endoplasmic reticulum (ER) and lysosome are central to cellular stress responses, but it is unclear how ER stress is signaled to lysosomes. Here the authors show that ER stress activates chaperone-mediated autophagy (CMA) via direct phosphorylation of the CMA receptor LAMP2A by the lysosomal p38 MAPK.

    • Wenming Li
    • , Jinqiu Zhu
    •  & Zixu Mao

  • Article
    | Open Access

    Lysosomal distribution is linked to the role of lysosomes in many cellular functions. Here the authors show that the lysosomal protein TMEM55B is regulated by TFEB and recruits JIP4 to the lysosomal surface inducing dynein-dependent transport of lysosomes toward the cell center in response to stress conditions.

    • Rose Willett
    • , José A. Martina
    •  & Rosa Puertollano

  • Article
    | Open Access

    Mutations in spermine synthase lead to Snyder-Robinson syndrome, a form of intellectual disability syndrome. Here the authors develop a Drosophila model of this disease, and show that lysosomal dysfunction and oxidative stress contribute to the morphological phenotype in these flies, as well as to cellular deficits in cells derived from patients.

    • Chong Li
    • , Jennifer M. Brazill
    •  & R. Grace Zhai

  • Article
    | Open Access

    Mutations in the granulin gene are associated with frontotemporal lobe dementia (FTLD) and a lysosomal storage disease. The authors show that reduced progranulin levels leads to impaired neuronal uptake and lysosomal delivery of prosaposin, and that decreased prosaposin expression in mice leads to FTLD-like behaviour.

    • Xiaolai Zhou
    • , Lirong Sun
    •  & Fenghua Hu

  • Article
    | Open Access

    Protein kinase A (PKA) is a key mediator of cyclic AMP signalling. Here, Eccles et al. show that ARHGAP36 antagonizes PKA by acting as a kinase inhibitor and targeting the catalytic subunit for endolysosomal degradation, thus reducing sensitivity of cells to cAMP and promoting Hedgehog signalling.

    • Rebecca L. Eccles
    • , Maciej T. Czajkowski
    •  & Oliver Rocks

  • Article
    | Open Access

    Reactive oxygen species (ROS) damage cell components, necessitating their clearance through autophagy. Here, the authors show that ROS can induce autophagy by triggering TRPML1 to release Ca2+from the lysosomal lumen, in turn activating the autophagy and lysosomal biogenesis regulator TFEB.

    • Xiaoli Zhang
    • , Xiping Cheng
    •  & Haoxing Xu

  • Article
    | Open Access

    In response to amino acid and growth factor removal the TSC1/2 complex translocates to the lysosome to inactivate mTOR and inhibit cell growth. Here, the authors have shown that other cellular stresses also trigger this translocation to the lysosome suggesting that this is a universal mechanism in the stress response.

    • Constantinos Demetriades
    • , Monika Plescher
    •  & Aurelio A. Teleman

  • Article
    | Open Access

    The human serum protein apolipoprotein L1 (APOL1) is taken up by trypanosomes where it triggers cell death, forming pores in endolysosomal membranes. Vanwalleghem et al.show that APOL1 triggers both lysosomal and mitochondrial membrane permeabilization, and that the latter is responsible for trypanolysis.

    • Gilles Vanwalleghem
    • , Frédéric Fontaine
    •  & Etienne Pays

  • Article
    | Open Access

    Essential amino acids such as leucine activate mTORC1 signalling after entering the lysosome, but the molecular basis for lysosomal amino-acid uptake is unclear. Here Milkereit et al. show that LAPTM4b, a lysosomal membrane protein, recruits a leucine transporter to the lysosome and promotes amino-acid influx and mTORC1 signalling.

    • Ruth Milkereit
    • , Avinash Persaud
    •  & Daniela Rotin

  • Article
    | Open Access

    BafilomycinA1 is an autophagy inhibitor, presumably owing to its blocking effect on the lysosomal proton pump V-ATPase. Here the authors show that V-ATPase-deficient lysosomes can still fuse with autophagosomes, showing that lysosomal acidification and fusion are two separable, independent events.

    • Caroline Mauvezin
    • , Péter Nagy
    •  & Thomas P. Neufeld

  • Article |

    Rag family proteins control activation of the mTORC1 complex at the lysosome. Here the authors show that loss of RagA/B causes cardiac hypertrophy in mice, revealing an mTORC-independent function of Rag GTPAses as regulators of lysosome function and autophagic flux in cardiomyocytes.

    • Young Chul Kim
    • , Hyun Woo Park
    •  & Kun-Liang Guan

  • Article |

    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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