Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Deformation of the continental lithosphere is traditionally modeled assuming that heat production in the subcontinental lithospheric mantle is negligible. Although this may be appropriate for highly depleted Archean lithosphere, studies of mantle xenoliths and lithospheric-derived mafic rocks suggest that heat productions of up to 0.4 ;μW/m3 may be attained in the mantle of Phanerozoic and Neoproterozoic regions due to modal metasomatism. To investigate the effect of a local enrichment in heat-producing elements within the lithospheric mantle on the continental deformation, we performed a series of 2D thermo-mechanical models simulating the deformation of a lithospheric plate 1000 km long, which contains in its central part a 200 km wide and 20 km-thick mantle layer with a heat production of 0.05;–0.25 ;μW/m3 between 40 and 80 km depth, leading to a local enhancement of the surface heat flow by 1;–5 mW/m2. Compression models show that a 20 km-thick layer with a heat production as low as 0.05 ;μW/m3 within the shallow lithospheric mantle leads to strain localization in both the enriched mantle and the overlying crust. Strain localization depends exponentially on the temperature increase in the lithosphere section, which is controlled by the volume of metasomatized mantle and the intensity of the metasomatic enrichment in heat-producing elements. A heat production of 0.25 μW/m3 between 60 and 80 km depth results, for instance, in strains within and above the metasomatized mantle 5 times higher than in the surrounding lithosphere. Strain localization also depends on the location of the heat-producing domain and on the plate rheological structure; deeper heat-producing domains and weaker plates leading to stronger localization. These results provide an explanation for strain localization in intraplate environments, leading to the formation of orogenic belts situated hundreds to thousands of kilometers away from known plate boundaries, as observed in the Neoproterozoic belts of Gondwana and in the present-day deformation of the Asian plate.
ISSN: 0012-821X

hal-00411386
https://hal.archives-ouvertes.fr/hal-00411386
DOI : 10.1016/j.epsl.2008.07.040