EyaHOST, a modular genetic system for investigation of intercellular and tumor-host interactions .

Unlabelled: Cell biology and genetic analysis of intracellular, intercellular and inter-organ interaction studies in animal models are key for understanding development, physiology, and disease. The MARCM technique can emulate tumor development by simultaneous clonal tumor suppressor loss-of-function generation coupled with GAL4-UAS-driven oncogene and marker expression, but the utility is limited for studying tumor-host interactions due to genetic constraints. To overcome this, we introduce EyaHOST, a novel system that replaces MARCM with the QF2-QUAS binary gene expression system under the promoter control, unleashing the fly community genome-wide GAL4-UAS driven tools to manipulate any host cells or tissue at scale.

Autophagy power expands: fuse those cells!

The lysosomal degradation pathway of autophagy depends on a set of evolutionarily conserved autophagy-related molecules (ATGs) bestowed with the power to direct membrane trafficking and biology. In this issue of EMBO Journal, Kakanj P et al reveal a surprising role for the autophagy machinery in cell fusion (Kakanj et al, 2022). Autophagy is physiologically required for cell syncytium formation through dismantling the lateral plasma membrane during wound healing, and unchecked autophagy can drive cell fusion in epithelial tissues without compromising epithelial integrity.

Computed tomography with segmentation and quantification of individual organs in a D. melanogaster tumor model.

Drosophila melanogaster tumor models are growing in popularity, driven by the high degree of genetic as well as functional conservation to humans. The most common method to measure the effects of a tumor on distant organs of a human cancer patient is to use computed tomography (CT), often used in diagnosing cachexia, a debilitating cancer-induced syndrome most visibly characterized by loss of muscle mass. Successful application of high resolution micro-CT scanning of D.

Host autophagy mediates organ wasting and nutrient mobilization for tumor growth.

During tumor growth-when nutrient and anabolic demands are high-autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling. Ras-driven tumors additionally invoke non-autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well-characterized malignant tumor model in Drosophila melanogaster.

NAD augmentation restores mitophagy and limits accelerated aging in Werner syndrome.

Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models.

Autophagy and Tumorigenesis in Drosophila.

The resurgence of Drosophila as a recognized model for carcinogenesis has contributed greatly to our conceptual advance and mechanistic understanding of tumor growth in vivo. With its powerful genetics, Drosophila has emerged as a prime model organism to study cell biology and physiological functions of autophagy. This has enabled exploration of the contributions of autophagy in several tumor models.

Microenvironmental autophagy promotes tumour growth.

As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues.

Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages.

Macrophages respond to changes in environmental stimuli by assuming distinct functional phenotypes, a phenomenon referred to as macrophage polarization. We generated classically (M1) and alternatively (M2) polarized macrophages--two extremes of the polarization spectrum--to compare the properties of their phagosomes. Specifically, we analyzed the regulation of the luminal pH after particle engulfment.