Regulation of Host-Pathogen Interactions via the Ubiquitin System.

Ubiquitination is a posttranslational modification that regulates a multitude of cellular functions. Pathogens, such as bacteria and viruses, have evolved sophisticated mechanisms that evade or counteract ubiquitin-dependent host responses, or even exploit the ubiquitin system to their own advantage. This is largely done by numerous pathogen virulence factors that encode E3 ligases and deubiquitinases, which are often used as weapons in pathogen-host cell interactions. Moreover, upon pathogen attack, host cellular signaling networks undergo major ubiquitin-dependent changes to protect the host cell, including coordination of innate immunity, remodeling of cellular organelles, reorganization of the cytoskeleton, and reprogramming of metabolic pathways to restrict growth of the pathogen. Here we provide mechanistic insights into ubiquitin regulation of host-pathogen interactions and how it affects bacterial and viral pathogenesis and the organization and response of the host cell.

A molecular toolbox for interrogation of membrane contact sites.

Membrane contact sites (MCSs) are specialized subcellular compartments formed by closely apposed membranes from two organelles. The intermembrane gap is separated by a distance ranging from 10 to 35 nm. MCSs are typically maintained through dynamic protein-protein and protein-lipid interactions. These intermembrane contact sites constitute important intracellular signalling hotspots to mediate a plethora of cellular processes, including calcium homeostasis, lipid metabolism, membrane biogenesis and organelle remodelling. In recent years, a series of genetically encoded probes and chemogenetic or optogenetic actuators have been invented to aid the visualization and interrogation of MCSs in both fixed and living cells. These molecular tools have greatly accelerated the pace of mechanistic dissection of membrane contact sites at the molecular level. In this review, we present an overview on the latest progress in this endeavour, and provide a general guide to the selection of methods and molecular tools for probing interorganellar membrane contact sites.

Peroxisome Plasticity at the Virus-Host Interface.

Peroxisomes are multifunctional organelles with roles in cellular metabolism, cytotoxicity, and signaling. The plastic nature of these organelles allows them to respond to diverse biological processes, such as virus infections, by remodeling their biogenesis, morphology, and composition to enhance specific functions. During virus infections in humans, peroxisomes act as important immune signaling organelles, aiding the host by orchestrating antiviral signaling. However, more recently it was discovered that peroxisomes can also benefit the virus, facilitating virus-host interactions that rewire peroxisomes to support cellular processes for virus replication and spread. Here, we describe recent studies that uncovered this double-edged character of peroxisomes during infection, highlighting mechanisms that viruses have coevolved to take advantage of peroxisome plasticity. We also provide a perspective for future studies by comparing the established roles of peroxisomes in plant infections and discussing the promise of virology studies as a venue to reveal the uncharted biology of peroxisomes.

Silencing the tobacco gene for RNA-dependent RNA polymerase 1 and infection by potato virus Y cause remodeling of cellular organelles.

RNA-dependent RNA polymerase 1 (RDR1) has been shown to be involved in DNA methylation, RNA silencing and regulating expression of other genes. RDR1 gene expression is stimulated by infection with potato virus Y° (PVY). Transgenic Nicotiana tabacum plants silenced for RDR1 gene expression showed morphological changes in mesophyll cells, associated with remodeling of the nuclei, chloroplasts and mitochondria. RDR1 silencing led to decreased nuclear size, increased heterochromatin content and aggregation, decreased numbers of chloroplasts, plus changes in shape, internal structures and integrity of chloroplasts and mitochondria. RDR1-silenced transgenic plants showed increased PVY accumulation and ultrastructural remodeling was intensified in both chloroplasts and mitochondria of PVY-infected, RDR1-silenced plants. By contrast, heterochromatin condensation was reduced by PVY infection, and in non-transgenic plants the nuclei were translucent and lacked morphology after PVY infection. Thus, RDR1 regulates gene expression leading to remodeling of chromosomes, and PVY infection counteracts these effects on chromosomal remodeling.