Biology subjects

Wase, N.

Publications and source records attributed to Wase, N..

4 recordsLinked to original sources

bioRxiv2025

Ampk alpha2 T172 Activation Dictates Exercise Performance and Energy Transduction in Skeletal Muscle

AMPK (5'-AMP-activated protein kinase) is an energetic sensor for metabolic regulation and integration. Here, we employed CRISPR/Cas9 to generate non-activatable Ampk knock-in (KI) mice with mutation of threonine 172 phosphorylation site to alanine, circumventing the limitations of previous genetic interventions that disrupt the protein stoichiometry. KI mice of Ampk2, but not Ampk1, demonstrated phenotypic changes with increased fat-to-lean mass, impaired endurance exercise capacity, and diminished mitochondrial maximal respiration and conductance in skeletal muscle. Integrated temporal multi-omic analysis (proteomics/phosphoproteomics/metabolomics) in skeletal muscle at rest and during exercise establishes a pleiotropic yet imperative role of Ampk2 T172 activation for glycolytic and oxidative metabolism, mitochondrial respiration, and contractile function. Importantly, there is a significant overlap of skeletal muscle proteomic changes in Ampk2 T172A KI mice with that of type 2 diabetic patients. Our findings suggest that Ampk2 T172 activation is critical for exercise performance and energy transduction in skeletal muscle and may serve as a therapeutic target for type 2 diabetes.

molecular biology↗

bioRxiv2023

Nitrogen starvation leads to TOR kinase-mediated downregulation of fatty acid synthesis in the algae Chlorella sorokiniana and Chlamydomonas reinhardtii

The accumulation of triacylglycerol (TAG) as a storage compound in eukaryotic algae has been the subject of extensive studies over the last 50 years. The model industrial alga Chlorella sorokiniana accumulates TAG and other storage compounds under nitrogen (N)-limited growth. Previously we used transcriptomics to explore the regulation of TAG synthesis in C. sorokiniana. Surprisingly, our analysis showed that the expression of several key genes encoding enzymes involved in plastidic fatty acid synthesis are significantly repressed. Metabolic labeling with radiolabeled acetate showed that de novo fatty acid synthesis is indeed downregulated under N-limitation. Likewise, inhibition of the Target of Rapamycin kinase (TOR), a key regulator of metabolism and growth, decreased fatty acid synthesis. We compared the changes in proteins and phosphoprotein abundance using a proteomics and phosphoproteomics approach in C. sorokiniana cells under N-limitation or TOR inhibition and found extensive overlap between the N-limited and TOR-inhibited conditions. We also identified changes in the phosphorylation levels of TOR complex proteins, TOR-kinase and RAPTOR, under N-limitation, indicating that TOR signaling is altered. Our results indicate that under N-limitation there is significant metabolic remodeling, including fatty acid synthesis, mediated by TOR signaling. We find that TOR-mediated metabolic remodeling of fatty acid synthesis under N-limitation is conserved in the chlorophyte algae Chlorella sorokiniana and Chlamydomonas reinhardtii.

plant biology↗

bioRxiv2021

The genome of stress tolerant crop wild relativePaspalum vaginatum leads to increased biomassproductivity in the crop Zea mays

A number of crop wild relatives can tolerate extreme stressed to a degree outside the range observed in their domesticated relatives. However, it is unclear whether or how the molecular mechanisms employed by these species can be translated to domesticated crops. Paspalum Paspalum vaginatum is a self-incompatible and multiply stress-tolerant wild relative of maize and sorghum. Here we describe the sequencing and pseudomolecule level assembly of a vegetatively propagated accession of P. vaginatum. Phylogenetic analysis based on 6,151 single-copy syntenic orthologous conserved in 6 related grass species placed paspalum as an outgroup of the maize-sorghum clade demonstrating paspalum as their closest sequenced wild relative. In parallel metabolic experiments, paspalum, but neither maize nor sorghum, exhibited significant increases in trehalose when grown under nutrient-deficit conditions. Inducing trehalose accumulation in maize, imitating the metabolic phenotype of paspalum, resulting in autophagy dependent increases in biomass accumulation.

plant biology↗

bioRxiv2021

Reactive oxygen species mediate thylakoid membrane remodeling and triacylglycerol synthesis under nitrogen starvation in the alga Chlorella sorokiniana

Many microbes accumulate energy storage molecules such as triglycerides and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study we show that accumulation of reactive oxygen species (ROS) under nitrogen limitation in the microalga Chlorella sorokiniana is involved in thylakoid membrane remodeling, leading to chlorosis. We show that ROS accumulation under nitrogen limitation is an active process involving downregulation of expression of ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase and amine oxidases. Expression of enzymes involved in ascorbate and glutathione metabolism are also affected under these conditions. Quenching ROS under nitrogen limitation reduces TAG accumulation, adding additional evidence for the role of ROS signaling in the process.

plant biology↗