The Importance of Participation in Regeneration of Peripheral Urban Spaces: the Experience of “Serpentone Reload”

Suburbs are often very contradictory places. Despite great part of urban population live there, these parts of cities are mostly considered as degradation places. The topic of suburbs regeneration is relevant today. Nevertheless, often expensive interventions implemented by local authorities fail to regenerate their public spaces, increasing the degradation condition. This paper presents the experience of “Serpentone reload”, a workshop based on participatory reactivation of abandoned or underused spaces and buildings in "Cocuzzo/Serpentone" neighbourhood in Potenza (Basilicata, Italy). The workshop particularly focused on the reuse of the "Ship", an underground building with a park coverage completed in 2010 and designed by the firm Archea. The "Ship" has been forgotten and not used for long time, not only by the neighbourhood, but by the whole citizenship, because it has been perceived as an extraneous element and the result of an imposition from the top, definitely not the outcome of shared choices. During the workshop, the "Ship" (“Nave” in Italian language) has become an art centre called N.Av.E. (New Expressive Adventures – Nuove Avventure Espressive in Italian), a place capable to host temporary events (expositions, lectures, theatre and dance performance, movies projection, etc.). Such a choice has allowed the neighbourhood and the city to take back that “object” so hated as ignored. The experience is particularly significant, because it shows how low cost interventions, realized with citizens involvement and participation, could contribute to the regeneration of peripheral urban areas more than expensive and complex imposed interventions, which often do not take into account dwellers real needs and expectations

Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis.

Autophagy has vasculoprotective roles, but whether and how it regulates lymphatic endothelial cells (LEC) homeostasis and lymphangiogenesis is unknown. Here, we show that genetic deficiency of autophagy in LEC impairs responses to VEGF-C and injury-driven corneal lymphangiogenesis. Autophagy loss in LEC compromises the expression of main effectors of LEC identity, like VEGFR3, affects mitochondrial dynamics and causes an accumulation of lipid droplets (LDs) in vitro and in vivo. When lipophagy is impaired, mitochondrial ATP production, fatty acid oxidation, acetyl-CoA/CoA ratio and expression of lymphangiogenic PROX1 target genes are dwindled. Enforcing mitochondria fusion by silencing dynamin-related-protein 1 (DRP1) in autophagy-deficient LEC fails to restore LDs turnover and lymphatic gene expression, whereas supplementing the fatty acid precursor acetate rescues VEGFR3 levels and signaling, and lymphangiogenesis in LEC-Atg5-/- mice. Our findings reveal that lipophagy in LEC by supporting FAO, preserves a mitochondrial-PROX1 gene expression circuit that safeguards LEC responsiveness to lymphangiogenic mediators and lymphangiogenesis.We thank K. Rillaerts, J. Souffreau, and A. Bouche, for expert technical support and Dr. A. Luttun and Dr. A. Zijsen for sharing tools and advices. P.A. is supported by grants from the Flemish Research Foundation (FWO-Vlaanderen; G076617N, G049817N, G070115N), the EOS MetaNiche consortium N degrees 40007532, Stichting tegen Kanker (FAF-F/2018/1252) and the iBOF/21/053 ATLANTIS consortium with G.B. D.H. is the recipient of an FWO Doctoral Fellowship from the Flemish Research Foundation (FWO-Vlaanderen, 1186019N), Belgium. M.B. is supported by the `Fonds voor Wetenschappelijk Onderzoek' (FWO). K.J. is the recipient of an FWO Postdoctoral Fellowship from the Flemish Research Foundation (FWO-Vlaanderen). P.C. is supported by Methusalem funding by the Flemish government, and by an ERC Advanced Research Grant (EU-ERC269073).S

Endoplasmic Reticulum Stress signalling - from basic mechanisms to clinical applications

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one-third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling-centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes

Staying in touch: Taking a closer look at ER-Golgi contact sites

ER-Golgi contact sites regulate lipid homeostasis and trafficking across the trans-Golgi network. However, their molecular nature is elusive. In this issue, Venditti et al. (2019. J. Cell Biol https://doi.org/10.1083/jcb.201812020 and https://doi.org/10.1083/jcb.201812021) shine new light on the molecular determinants coupling lipid exchange and cargo exit with maintenance of ER-Golgi contacts.status: publishe

Mitochondria-Associated Membranes As Networking Platforms and Regulators of Cancer Cell Fate

The tight cross talk between two essential organelles of the cell, the endoplasmic reticulum (ER) and mitochondria, is spatially and functionally regulated by specific microdomains known as the mitochondria-associated membranes (MAMs). MAMs are hot spots of Ca2+ transfer between the ER and mitochondria, and emerging data indicate their vital role in the regulation of fundamental physiological processes, chief among them mitochondria bioenergetics, proteostasis, cell death, and autophagy. Moreover, and perhaps not surprisingly, it has become clear that signaling events regulated at the ER–mitochondria intersection regulate key processes in oncogenesis and in the response of cancer cells to therapeutics. ER–mitochondria appositions have been shown to dynamically recruit oncogenes and tumor suppressors, modulating their activity and protein complex formation, adapt the bioenergetic demand of cancer cells and to regulate cell death pathways and redox signaling in cancer cells. In this review, we discuss some emerging players of the ER–mitochondria contact sites in mammalian cells, the key processes they regulate and recent evidence highlighting the role of MAMs in shaping cell-autonomous and non-autonomous signals that regulate cancer growth

Interactome Analysis of the ER Stress Sensor Perk Uncovers Key Components of ER-Mitochondria Contact Sites and Ca Signalling

We recently reported that the ER stress kinase PERK regulates ER-mitochondria appositions and ER– plasma membrane (ER-PM) contact sites, independent of its canonical role in the unfolded protein response. PERK regulation of ER-PM contacts was revealed by a proximity biotinylation (BioID) approach and involved a dynamic PERK-Filamin A interaction supporting the formation of ER-PM contacts by actin-cytoskeleton remodeling in response to depletion of ER-Ca 2+ stores. In this report, we further interrogated the PERK BioID interactome by validating through co-IP experiments the interaction between PERK and two proteins involved in Ca 2+ handling and ER-mitochondria contact sites. These included the vesicle associated membrane (VAMP)-associated proteins (VAPA/B) and the main ER Ca 2+ pump sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2). These data identify new putative PERK interacting proteins with a crucial role in membrane contact sites and Ca 2+ signaling further supporting the uncanonical role of PERK in Ca 2+ signaling through membrane contact sites (MCSs)

Trial Watch: Immunogenic cell death induction by anticancer chemotherapeutics

The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.status: publishe

The Importance of Participation in Regeneration of Peripheral Urban Spaces: the Experience of “Serpentone Reload”

Suburbs are often very contradictory places. Despite great part of urban population live there, these parts of cities are mostly considered as degradation places. The topic of suburbs regeneration is relevant today. Nevertheless, often expensive interventions implemented by local authorities fail to regenerate their public spaces, increasing the degradation condition. This paper presents the experience of “Serpentone reload”, a workshop based on participatory reactivation of abandoned or underused spaces and buildings in "Cocuzzo/Serpentone" neighbourhood in Potenza (Basilicata, Italy). The workshop particularly focused on the reuse of the "Ship", an underground building with a park coverage completed in 2010 and designed by the firm Archea. The "Ship" has been forgotten and not used for long time, not only by the neighbourhood, but by the whole citizenship, because it has been perceived as an extraneous element and the result of an imposition from the top, definitely not the outcome of shared choices. During the workshop, the "Ship" (“Nave” in Italian language) has become an art centre called N.Av.E. (New Expressive Adventures – Nuove Avventure Espressive in Italian), a place capable to host temporary events (expositions, lectures, theatre and dance performance, movies projection, etc.). Such a choice has allowed the neighbourhood and the city to take back that “object” so hated as ignored. The experience is particularly significant, because it shows how low cost interventions, realized with citizens involvement and participation, could contribute to the regeneration of peripheral urban areas more than expensive and complex imposed interventions, which often do not take into account dwellers real needs and expectation

“Serpentone Reload” an Experience of Citizens Involvement in Regeneration of Peripheral Urban Spaces

Suburbs are often very contradictory places. Despite great part of urban population live there, these parts of cities are mostly considered as degradation places. The topic of suburbs regeneration is relevant today. Nevertheless, often expensive interventions implemented by local authorities fail to regenerate their public spaces. This paper presents the experience of “Serpentone reload”, a workshop based on participatory reactivation of abandoned or underused spaces and buildings in “Cocuzzo/Serpentone” neighbourhood in Potenza (Basilicata, Italy). The workshop particularly focused on the reuse of the “Ship”, an underground building, completed in 2010, never used, because it has been perceived as an extraneous element, the result of an imposition and not the outcome of shared choices. The experience is particularly significant, because it shows how low cost interventions, realized with citizens involvement, could contribute to the regeneration of peripheral urban areas more than expensive and complex imposed interventions