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Mitochondrial division is not an autonomous event but involves multiple organelles, including the endoplasmic reticulum (ER) and lysosomes. Whereas the ER drives the constriction of mitochondrial membranes, the role of lysosomes in mitochondrial division is not known. Here, using super-resolution live-cell imaging, we investigate the recruitment of lysosomes to the site of mitochondrial division. We find that the ER recruits lysosomes to the site of division through the interaction of VAMP-associated proteins (VAPs) with the lysosomal lipid transfer protein ORP1L to induce a three-way contact between the ER, lysosome, and the mitochondrion. We also show that ORP1L might transport phosphatidylinositol-4-phosphate (PI(4)P) from lysosomes to mitochondria, as inhibiting its transfer or depleting PI(4)P at the mitochondrial division site impairs fission, demonstrating a direct role for PI(4)P in the division process. Our findings support a model where the ER recruits lysosomes to act in concert at the fission site for the efficient division of mitochondria. Membrane contact sites between organelles have specialized functions that are only beginning to be understood. Here, the authors show that ORP1L mediates lysosome recruitment and PI(4)P signaling at endoplasmic reticulum-lysosome-mitochondria three-way contact sites involved in mitochondrial division.

Purpose of ReviewHereditary spastic paraplegias are a genetically heterogeneous group of neurological disorders. Patients present lower limb weakness and spasticity, complicated in complex forms by additional neurological signs. We review here the major steps toward understanding the molecular basis of these diseases made over the last 10 years.Recent FindingsOur perception of the intricate connections between clinical, genetic, and molecular aspects of neurodegenerative disorders has radically changed in recent years, thanks to improvements in genetic approaches. This is particularly true for hereditary spastic paraplegias, for which > 60 genes have been identified, highlighting (i) the considerable genetic heterogeneity of this group of clinically diverse disorders, (ii) the fuzzy border between recessive and dominant inheritance for several mutations, and (iii) the overlap of these mutations with other neurological conditions in terms of their clinical effects. Several hypotheses have been put forward concerning the pathophysiological mechanisms involved, based on the genes implicated and their known function and based on studies on patient samples and animal models. These mechanisms include mainly abnormal intracellular trafficking, changes to endoplasmic reticulum shaping and defects affecting lipid metabolism, lysosome physiology, autophagy, myelination, and development. Several causative genes affect multiple of these functions, which are, most of the time, interconnected.SummaryRecent major advances in our understanding of these diseases have revealed unifying pathogenic models that could be targeted in the much-needed development of new treatments.

The endoplasmic reticulum (ER) forms contacts with the lysosomal compartment, regulating lysosome positioning and motility. The movements of lysosomes are controlled by the attachment of molecular motors to their surface. However, the molecular mechanisms by which ER controls lysosome dynamics are still elusive. Here, using mouse brain extracts and mouse embryonic fibroblasts, we demonstrate that spatacsin is an ER-resident protein regulating the formation of tubular lysosomes, which are highly dynamic. Screening for spatacsin partners required for tubular lysosome formation showed spatacsin to act by regulating protein degradation. We demonstrate that spatacsin promotes the degradation of its partner AP5Z1, which regulates the relative amount of spastizin and AP5Z1 at lysosomes. Spastizin and AP5Z1 contribute to regulate tubular lysosome formation, as well as their trafficking by interacting with anterograde and retrograde motor proteins, kinesin KIF13A and dynein/dynactin subunit p150 Glued , respectively. Ultimately, investigations in polarized mouse cortical neurons in culture demonstrated that spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking. Collectively, our results identify spatacsin as a protein regulating the directionality of lysosome trafficking.

Bien qu’il n’existe pas à proprement parler de régime différencié concernant le foncier irrigué en Birmanie, le développement de l’irrigation se confond dans la majorité des cas avec le développement de la riziculture inondée, et en ce sens génère des enjeux fonciers qui lui sont propres. L’étude du rapport des pouvoirs birmans pré- et postcoloniaux à l’irrigation permet de mettre en exergue la continuité symbolique et politique de la relation entre maîtrise de l’irrigation à des fins de riziculture et construction étatique. L’intervention des gouvernements postcoloniaux en matière d’irrigation peut être caractérisée d’une part en politiques de contrôle dans les plaines centrales et dans le delta de l’Irrawaddy, et en politiques d’ordre « civilisatrices » dans les régions montagneuses d’autre part. Bien que de natures différentes, les formes d’insécurité foncière liées à la culture de terres irriguées n’en sont pas moins une constante. Dans les régions de plus fort contrôle de l’État (c’est-à-dire dans les grands périmètres irrigués des plaines et du delta), la sécurité foncière qui pourrait théoriquement découler de régimes fonciers stables a en réalité été systématiquement sapée par les contraintes économiques imposées dans un objectif d’accroissement de la productivité pour l’État et au détriment des petits agriculteurs. Dans les hautes terres, l’introduction de programmes de culture du riz irrigué a profondément bouleversé les régimes fonciers coutumiers et conduit à la captation des terres les plus fertiles par une élite. Although, strictly speaking, there is no differentiated tenure regime concerning irrigated land in Myanmar, the development of irrigation coincides, in most cases, to the development of flooded rice cultivation, and as such generates specific land issues. The study of the relationship between pre- and post-colonial Burmese powers and irrigation highlights the symbolic and political continuity of the relationship between irrigation control for rice cultivation and State construction. Post-colonial government intervention in irrigation can be characterized as control policies in the central plains and the Irrawaddy Delta on the one hand, and as ’civilizing’ policies in the mountainous regions on the other. Although different in nature, the forms of land insecurity linked to irrigated land cultivation are nonetheless a constant. In areas of greater state control ( i.e. , the large irrigated areas of the plains and delta), land tenure security that could theoretically be derived from stable land tenure regimes has in reality been systematically undermined by economic constraints that were imposed in relation to the objective of increasing productivity for the State and to the detriment of small farmers. In the highlands, the introduction of irrigated rice programs has profoundly disrupted customary land tenure and led to the capture of the most fertile land by an elite.

Mutations in SPG11 , leading to loss of spatacsin function, impair the formation of membrane tubules in lysosomes and cause lysosomal lipid accumulation. However, the full nature of lipids accumulating in lysosomes and the physiological consequences of such accumulation are unknown. Here we show that loss of spatacsin inhibits the formation of tubules on lysosomes and prevents the clearance of cholesterol from this subcellular compartment. Accumulation of cholesterol in lysosomes decreases cholesterol levels in the plasma membrane, enhancing the entry of extracellular calcium by store-operated calcium entry and increasing resting cytosolic calcium levels. Higher cytosolic calcium levels promote the nuclear translocation of the master regulator of lysosomes TFEB, preventing the formation of tubules and the clearance of cholesterol from lysosomes. Our work reveals a homeostatic balance between cholesterol trafficking and cytosolic calcium levels and shows that loss of spatacsin impairs this homeostatic equilibrium. Boutry et al. show that the loss of spatacsin prevents the clearance of cholesterol from lysosomes by inhibiting the formation of tubules in this compartment. Accumulation of cholesterol in lysosomes increases resting cytosolic calcium levels, promoting translocation of master regulator of lysosome function TFEB.

The Moken are a sea-nomadic population living in the Mergui Archipelago, where they remained out of the reach of the state while developing clientelist relationships with dominant societies over several centuries. Starting in the mid-twentieth century, economic development and Burmese colonization of the islands led the Moken to face major transformations of their territory and way of life. This article takes a long-term approach to understanding Moken resilience by examining their oral literature, rituals and mobility developed in connection to the populations they live alongside. It shows that the Moken have maintained a core nomadic identity that enabled them to develop clientelist relationships throughout successive historical eras.

The Moken are a sea-nomadic population living in the Mergui Archipelago, where they remained out of the reach of the state while developing clientelist relationships with dominant societies over several centuries. Starting in the mid-twentieth century, economic development and Burmese colonization of the islands led the Moken to face major transformations of their territory and way of life. This article takes a long-term approach to understanding Moken resilience by examining their oral literature, rituals and mobility developed in connection to the populations they live alongside. It shows that the Moken have maintained a core nomadic identity that enabled them to develop clientelist relationships throughout successive historical eras.

The prospect of imminent tourism development of the Mergui Archipelago (Myanmar) has generated various processes of cultural valorisation and heritage development of the Moken environment and culture, ranging from the involvement of these sea nomads in marine protected areas to the manufacturing of handicrafts for the tourist industry. The first attempts to commercialise their culture echo the stakes and expectations of the various actors involved in the development arena of the archipelago (Burmese fishermen, tourism entrepreneurs, NGOs, government). In this context, and at the request of the Moken, the authors developed a participatory project of Mapping their Social Space (CartES), which explores the collective knowledge (constructed and transmitted through oral literature) relating to the anthropisation of the territory. The CartES project aims to construct an identity representation with and for the Moken, the museum transposition of which shall reflect the complexity of the material and ideal interrelationships between society and its natural environment. At the crossroads of anthropology and museology, this article explores the scope and limitations of this approach, focusing on the analysis of the dynamics of expression, adhesion and conflict with regard to the production of a Moken patrimony and the identity dynamics it generates.

The humanitarian response to the disaster caused by Cyclone Nargis that hit the Ayeyarwady Delta region of Myanmar in 2008 is a pertinent example of a very specific phase in humanitarian response at the transition between emergency and development. The author shows that this phase, known as 'early recovery', being built on the specific characteristics of the emergency (lack of time and lack of means and input) and oriented towards development, is one in which the humanitarian aid agency is relatively restricted to the humanitarian sphere itself. As a result, the ideological discourse lengthily denounced by the post-structuralist anthropology of development – as a set of Western values imposed on the 'developing' countries to assert a new form of dominion – is actually powerful and quasi-monolithic in shaping the consequences of humanitarian aid. While there is no 'arena' for the 'beneficiaries' to discuss the aid's agency, a 'methodological populism' approach reveals, on the one hand, the antagonisms between a humanitarian ideology conveying considerations such as 'horizontal' communities versus 'hierarchical bonds' and, on the other, the similarity of its socioeconomic consequences on the Delta's society to those of the British colonial period.