Biology subjects

Tennessen, J.

Publications and source records attributed to Tennessen, J..

2 recordsLinked to original sources

bioRxiv2023

Wolbachia is a nutritional symbiont

The intracellular bacterium Wolbachia is a common symbiont of many arthropods and nematodes, well studied for its impacts on host reproductive biology. However, its broad success as a vertically transmitted infection cannot be attributed to manipulations of host reproduction alone. Using the Drosophila melanogaster model and their natively associated Wolbachia strain "wMel", we show that Wolbachia infection supports fly development and buffers against nutritional stress. Wolbachia infection across several fly genotypes and a range of nutrient conditions resulted in reduced pupal mortality, increased adult emergence, and larger size. We determined that the exogenous supplementation of pyrimidines partially rescued developmental phenotypes in the Wolbachia-free flies, and that Wolbachia titers were responsive to reduced gene expression of the flys de novo pyrimidine synthesis pathway. In parallel, transcriptomic and metabolomic analyses indicated that Wolbachia impacts larval biology far beyond pyrimidine metabolism. Wolbachia-infected larvae had strong signatures of shifts in glutathione and mitochondrial metabolism, plus significant changes in the expression of key developmental regulators including Notch, the insulin receptor (lnR), and the juvenile hormone receptor Methoprene-tolerant (Met). We propose that Wolbachia acts as a beneficial symbiont to support fly development and enhance host fitness, especially during periods of nutrient stress. SIGNIFICANCEWolbachia is a bacterial symbiont of arthropods and nematodes, well described for its manipulations of arthropod reproduction. However, many have theorized there must be more to this symbiosis, even in well-studied Wolbachia-host relationships such as with Drosophila. Reproductive impacts alone cannot explain the success and ubiquity of this bacterium. Here, we use Drosophila melanogaster and their native Wolbachia infections to show that Wolbachia supports fly development and significantly buffers flies against nutritional stress. These developmental advantages might help explain the ubiquity of Wolbachia infections.

developmental biology↗

bioRxiv2022

NMNAT2 is the major NAD+ provider for vesicular glycolysis generating on-board energy for fast axonal transport cargos

BackgroundBioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimers, Parkinsons and Huntingtons disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose far-projecting axons are vulnerable to neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring proper axonal ATP levels for axonal transport, a critical function of axons. MethodsWe generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting NAD hydrolase sterile alpha and TIR motif-containing protein 1 (SARM1) prevented axonal deficits caused by NMNAT2 loss. Our study used a combination of genetic, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos application. ResultsWe provide in vivo evidence that NMNAT2 in cortical glutamatergic neurons is required for axonal survival. Using in vivo and in vitro studies we demonstrate that NMNAT2 protects axons by ensuring the proper NAD-redox potential in distal axons of cortical neurons to support glycolysis on vesicular cargos, thus ensuring "onboard" ATP production fueling axonal transport. Exogenous NAD+ supplementation to NMNAT2 KO cortical neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate both in vitro and in vivo that reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons. ConclusionNMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.

neuroscience↗