HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

Developpement d'un systeme d'aide a la gestion des canaux d'irrigation. In FrenchDeveloping a system to help manage irrigation canals

The aim of this 3 months training course was to re-program and develop an irrigation management information system created in 1992 for local use in Sri Lanka. The main points of the new version are: ability to manage and to have hydraulic simulations via SIC on a network of branched canals; much more user friendly; direct application is possible in several parts of Pakistan, facilities for installation and opportunities to adapt. After a short description of the background, this report studies the global interest of computerizing an information system for irrigation canal management. Part 3 explains in the main what data are required and how they are stored in tables. Part 4 advises a list of further improvements

Lattice Parsing for Speech Recognition

A lot of work remains to be done in the domain of a better integration of speech recognition and language processing systems. This paper gives an overview of several strategies for integrating linguistic models into speech understanding systems and investigates several ways of producing sets of hypotheses that include more “semantic” variability than usual language models. The main goal is to present and demonstrate by actual experiments that sequential coupling may be efficiently achieved by word-lattice syntactic analyzers, efficiently parsing the huge number of hypothesis (i.e. possible sentences) contained in the lattice produced by the speech recognizer

Nix is a selective autophagy receptor for mitochondrial clearance

Autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. Recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. Yet, the specificity in targeting a particular substrate to the autophagy pathway remains poorly understood. Here, we show that the mitochondrial protein Nix is a selective autophagy receptor by binding to LC3/GABARAP proteins, ubiquitin-like modifiers that are required for the growth of autophagosomal membranes. In cultured cells, Nix recruits GABARAP-L1 to damaged mitochondria through its amino-terminal LC3-interacting region. Furthermore, ablation of the Nix:LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes. Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation