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Cell non-autonomous proteostasis regulation in aging and disease

Funding: This study was supported by the “Programa Operacional Regional de Lisboa-FEDER/ Project 02/SAICT/2020/072552,” and iNOVA4Health – UIDB/04462/2020 and UIDP/04462/2020, and by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), two programs financially supported by Fundação para a Ciência e Tecnologia / Ministério da Ciência, Tecnologia e Ensino Superior.; Aging is a risk factor for a number of disease...

LAMP2A regulates the loading of proteins into exosomes

Exosomes are extracellular vesicles of endosomal origin that are released by practically all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs, and proteins between different cells, tissues, or organs. Here, we describe a mechanism whereby proteins containing a KFERQ motif pentapeptide are loaded into a subpopulation of exosomes in a process t...

The Role of Biobanks in the Fight against COVID-19 Pandemic

Funding Information: FUNDING SOURCES MÉDRTUG CHAIN Biobank: Fundação para a Ciência e Tecnologia (FCT) for CHRC funding -UID/04923/2020. CHUPorto: Fundação para a Ciência e Tecnologia (FCT) Grant nº 2P29O (Research 4 COVID-19).

Ischaemia alters the effects of cardiomyocyte-derived extracellular vesicles on...

We thank Dr Nuno Alves (Cardiology Department, CHUC‐HG) who performed the collection of human blood samples and Doctor Francisco Caramelo (iCBR/FMUC) for helping with the statistical analysis. This work was supported by the European Regional Development Fund (ERDF) through the Operational Program for Competitiveness Factors (COMPETE) [under the projects PAC “NETDIAMOND” POCI‐01‐0145‐FEDER‐016385; HealthyAging20...

Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis

Deregulation of proteostasis is a main feature of many age-related diseases, often leading to the accumulation of toxic oligomers and insoluble protein aggregates that accumulate intracellularly or in the extracellular space. To understand the mechanisms whereby toxic or otherwise unwanted proteins are secreted to the extracellular space, we inactivated the quality-control and proteostasis regulator ubiquitin l...

Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angi...

Funding Information: This work was supported by European Regional Development Fund (FEDER) through the Operational Program for Competitiveness Factors (COMPETE) [HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323, POCI-01-0145-FEDER-016385, POCI-01-0145-FEDER-007440 to CNC.IBILI, POCI-01-0145-FEDER-007274 to i3S/INEB and NORTE-01-0145-FEDER-000012 to T.L.L.]; national funds through the Portuguese Foundation for...

Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the an...

Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the mos...

Erratum

K63 linked ubiquitin chain formation is a signal for HIF1A degradation by Chape...

We thank Dr. Ana Maria Cuervo for providing the shRNA against Lamp2a and Dr. Cam Patterson for the wild-type and mutant STUB1 constructs. This work was supported by grants from the Portuguese Foundation for Science and Technology (FCT), PTDC/SAU-ORG/113542/2009, PTDC/SAU-ORG/118694/2010, PEST-C/SAU/UI3282/2011-COMPETE and UID/NEU/04539/2013 from FCT.; Chaperone-Mediated Autophagy is a selective form of autophag...

STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy

The transcription factor HI F1 is mostly regulated by the oxygen-dependent proteasomal degradation of the labile subunit HI F1A. Recent data showed degradation of HI F1A in the lysosome through chaperone-mediated autophagy (CMA). However the molecular mechanism involved has not been elucidated. This study shows that the KFER Q-like motif, that has been identified in all CMA substrates, is required to mediate th...