AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1

Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways

Five characteristics of youth unemployment in Europe

Current levels of youth unemployment need to be understood in the context of increased labor market flexibility, an expansion of higher education, youth migration, and family legacies of long-term unemployment. Compared with previous recessions, European-wide policies and investments have significantly increased with attempts to support national policies. By mapping these developments and debates, we illustrate the different factors shaping the future of European labor markets. We argue that understanding youth unemployment requires a holistic approach that combines an analysis of changes in the economic sphere around labor market flexibility, skills attainment, and employer demand, as well as understanding the impact of family legacies affecting increasingly polarized trajectories for young people today. The success of EU policy initiatives and investments will be shaped by the ability of national actors to implement these effectively

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

British Household Panel Survey Harmonised Union Histories, 1991-2006

<p>Abstract copyright UK Data Service and data collection copyright owner.</p>This project used data from the <i>British Household Panel Survey</i> (BHPS) (available at the UKDA under SN 5151), to compile a dataset of variables relating to the starting, ending date and type of each union (cohabitation or legal marriage) of members of the BHPS. Evidence derived from the answers provided by both partners at each wave has been used. The dataset has been created on the basis of Chiara Pronzato's project which reconstructed union and childbirth histories from both retrospective and annual interviews (available at the UKDA under SN 5629). <br> <br> Further information about the project is available from the ESRC's <a href="http://www.esrc.ac.uk/my-esrc/grants/RES-061-23-0127/read" title ="Are storks striking for a contract renewal? Childbirth under changing employment, family and welfare arrangements">Are storks striking for a contract renewal? Childbirth under changing employment, family and welfare arrangements</a> award webpage.<br><B>Main Topics</B>:<br>Inconsistencies across answers provided by both partners or across time, as well as missing information found in those data with respect to the union histories of respondents has been corrected and harmonized, where possible. Both original data and proposed corrections are maintained to grant researchers the option to revert each choice (details about the guiding principles followed are to be found in the documentation). The dataset also contains a single identifier for each union (between the same two partners) ever present (and identified) in at least one wave of the panel