The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response.

Organisms use several strategies to mitigate mitochondrial stress, including the activation of the mitochondrial unfolded protein response (UPRmt). The UPRmt in Caenorhabditis elegans, regulated by the transcription factor ATFS-1, expands on this recovery program by inducing an antimicrobial response against pathogens that target mitochondrial function. Here, we show that the mammalian ortholog of ATFS-1, ATF5, protects the host during infection with enteric pathogens but, unexpectedly, by maintaining the integrity of the intestinal barrier. Intriguingly, ATF5 supports intestinal barrier function by promoting a satiety response that prevents obesity and associated hyperglycemia. This consequently averts dysregulated glucose metabolism that is detrimental to barrier function. Mechanistically, we show that intestinal ATF5 stimulates the satiety response by transcriptionally regulating the gastrointestinal peptide hormone cholecystokinin, which promotes the secretion of the hormone leptin. We propose that ATF5 protects the host from enteric pathogens by promoting intestinal barrier function through a satiety-response-mediated metabolic control mechanism.

On the offense and defense: mitochondrial recovery programs amidst targeted pathogenic assault.

Bacterial pathogens employ a variety of tactics to persist in their host and promote infection. Pathogens often target host organelles in order to benefit their survival, either through manipulation or subversion of their function. Mitochondria are regularly targeted by bacterial pathogens owing to their diverse cellular roles, including energy production and regulation of programmed cell death. However, disruption of normal mitochondrial function during infection can be detrimental to cell viability because of their essential nature. In response, cells use multiple quality control programs to mitigate mitochondrial dysfunction and promote recovery. In this review, we will provide an overview of mitochondrial recovery programs including mitochondrial dynamics, the mitochondrial unfolded protein response (UPRmt ), and mitophagy. We will then discuss the various approaches used by bacterial pathogens to target mitochondria, which result in mitochondrial dysfunction. Lastly, we will discuss how cells leverage mitochondrial recovery programs beyond their role in organelle repair, to promote host defense against pathogen infection.

Uncovering a mitochondrial unfolded protein response in corals and its role in adapting to a changing world.

The Anthropocene will be characterized by increased environmental disturbances, leading to the survival of stress-tolerant organisms, particularly in the oceans, where novel marine diseases and elevated temperatures are re-shaping ecosystems. These environmental changes underscore the importance of identifying mechanisms which promote stress tolerance in ecologically important non-model species such as reef-building corals. Mitochondria are central regulators of cellular stress and have dedicated recovery pathways including the mitochondrial unfolded protein response, which increases the transcription of protective genes promoting protein homeostasis, free radical detoxification and innate immunity. In this investigation, we identify a mitochondrial unfolded protein response in the endangered Caribbean coral Orbicella faveolata, by performing in vivo functional replacement using a transcription factor (Of-ATF5) originating from a coral in the model organism Caenorhabditis elegans. In addition, we use RNA-seq network analysis and transcription factor-binding predictions to identify a transcriptional network of genes likely to be regulated by Of-ATF5 which is induced during the immune challenge and temperature stress. Overall, our findings uncover a conserved cellular pathway which may promote the ability of reef-building corals to survive increasing levels of environmental stress.

Temperature Dependence of the Proteome Profile of the Psychrotolerant Pathogenic Food Spoiler Bacillus weihenstephanensis Type Strain WSBC 10204.

Bacillus weihenstephanensis is a subspecies of the Bacillus cereus sensu lato group of spore-forming bacteria known to cause food spoilage or food poisoning. The key distinguishing phenotype of B. weihenstephanensis is its ability to grow below 7 °C or, from a food safety perspective, to grow and potentially produce toxins in a refrigerated environment. Comparison of the proteome profile of B. weihenstephanensis upon its exposure to different culturing conditions can reveal clues to the mechanistic basis of its psychrotolerant phenotype as well as elucidate relevant aspects of its toxigenic profile. To this end, the genome of the type strain B. weihenstephanensis WSBC 10204 was sequenced and annotated. Subsequently, the proteome profiles of cells grown at either 6 or 30 °C were compared, which revealed considerable differences and indicated several hundred (uncharacterized) proteins as being subproteome- and/or temperature-specific. In this manner, several processes were newly indicated to be dependent on growth temperature, such as varying carbon flux routes and a different role for the urea cycle. Furthermore, a possible post-translational regulatory function for acetylation was suggested. Toxin production was determined to be largely independent of growth temperature.