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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Effects of Perfluorinated Alkyl Substances (PFAS) on Amphibian Body and Liver Conditions: Is Lipid Metabolism Being Perturbed throughout Metamorphosis?

Per- and polyfluoroalkyl substances (PFAS) may interact with peroxisome proliferator activated receptors (PPARs) and alter lipid homeostasis. Using Xenopus laevis, we investigated the effect of PFAS on (a) lipid homeostasis and whether this correlated to changes in body and hepatic condition; (b) the expression of hepatic genes regulated by PPAR; and (c) the hepatic lipidome. We chronically exposed tadpoles to 0.5 µg/L of either PFOS, PFHxS, PFOA, PFHxA, a binary mixture of PFOS and PFHxS (0.5 µg/L of each), or a control, from NF stage 52 through metamorphic climax. Growth, development, and survival were not affected, but we detected a sex-specific decrease in body condition at NF 66 (6.8%) and in hepatic condition (16.6%) across metamorphic climax for male tadpoles exposed to PFOS. We observed weak evidence for the transient downregulation of apolipoprotein-V (apoa5) at NF 62 in tadpoles exposed to PFHxA. Acyl-CoA oxidase 1 (acox1) was downregulated only in males exposed to PFHxS (Ln(Fold Change) = −0.54). We detected PFAS-specific downregulation of structural glycerophospholipids, while semi-quantitative profiling detected the upregulation in numerous glycerophospholipids, sphingomyelins, and diglycerides. Overall, our findings indicate that PFAS can induce sex-specific effects that change across larval development and metamorphosis. We demonstrate that PFAS alter lipid metabolism at environmentally relevant concentrations through divergent mechanisms that may not be related to PPARs, with an absence of effects on body condition, demonstrating the need for more molecular studies to elucidate mechanisms of PFAS-induced lipid dysregulation in amphibians and in other taxa.

Bushong, Anna (ORCID:0000000249630578)↗
DOE OSTI2024

Environment-specific virocell metabolic reprogramming

Abstract Viruses impact microbial systems through killing hosts, horizontal gene transfer, and altering cellular metabolism, consequently impacting nutrient cycles. A virus-infected cell, a “virocell,” is distinct from its uninfected sister cell as the virus commandeers cellular machinery to produce viruses rather than replicate cells. Problematically, virocell responses to the nutrient-limited conditions that abound in nature are poorly understood. Here we used a systems biology approach to investigate virocell metabolic reprogramming under nutrient limitation. Using transcriptomics, proteomics, lipidomics, and endo- and exo-metabolomics, we assessed how low phosphate (low-P) conditions impacted virocells of a marine Pseudoalteromonas host when independently infected by two unrelated phages (HP1 and HS2). With the combined stresses of infection and nutrient limitation, a set of nested responses were observed. First, low-P imposed common cellular responses on all cells (virocells and uninfected cells), including activating the canonical P-stress response, and decreasing transcription, translation, and extracellular organic matter consumption. Second, low-P imposed infection-specific responses (for both virocells), including enhancing nitrogen assimilation and fatty acid degradation, and decreasing extracellular lipid relative abundance. Third, low-P suggested virocell-specific strategies. Specifically, HS2-virocells regulated gene expression by increasing transcription and ribosomal protein production, whereas HP1-virocells accumulated host proteins, decreased extracellular peptide relative abundance, and invested in broader energy and resource acquisition. These results suggest that although environmental conditions shape metabolism in common ways regardless of infection, virocell-specific strategies exist to support viral replication during nutrient limitation, and a framework now exists for identifying metabolic strategies of nutrient-limited virocells in nature.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

A multi-omic characterization of the physiological responses to salt stress in Scenedesmus obliquus UTEX393

Scenedesmus obliquus UTEX393 is a promising microalgal candidate for sustainable biomanufacturing but its limited halotolerance hinders large-scale cultivation in saline environments. To investigate the molecular basis of salt stress responses, we conducted a comprehensive multi-omic analysis integrating genomics, transcriptomics, proteomics, lipidomics, metabolomics, and DNA affinity purification sequencing (DAP-seq). An improved nuclear genome assembly and annotation yielded 19,017 gene models and a 97% BUSCO completeness score, enabling construction of a genome-scale metabolic model. Comparing 15 ppt salinity stress to 5 ppt control, growth and productivity were significantly reduced, accompanied by widespread transcriptomic and proteomic changes. Transcriptomic analysis revealed downregulation of photosynthetic machinery and energy conservation genes, and upregulation of stress-responsive elements such as expansins, flavodoxins, and osmoprotectants. Lipidomic profiling showed accumulation of triacylglycerols (TAGs) and degradation of galactosyl lipids, consistent with a shift toward lipid biosynthesis to mitigate redox imbalance. Depletion of key polar metabolites and branched-chain amino acids suggested a rerouting of central carbon metabolism under stress. DAP-seq identified key transcription factors, including LHY1 and SPL12, that target central metabolic enzymes involved in redox balancing, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and malate dehydrogenase (MDH). These findings establish a regulatory-metabolic framework linking redox stress to lipid accumulation and reveal potential engineering targets to enhance salt tolerance. Overall, the multi-omic analysis supports the “overflow” hypothesis, where impaired photosynthesis results in excess reducing equivalents being diverted into TAG synthesis and highlights transcriptional regulators as candidates for improving algal robustness in brackish environments.

09 BIOMASS FUELS↗
DOE OSTI2021

The Role of Sugar Signaling in Regulating Plant Fatty Acid Synthesis

Photosynthates such as glucose, sucrose, and some of their derivatives play dual roles as metabolic intermediates and signaling molecules that influence plant cell metabolism. Such sugars provide substrates for de novo fatty acid (FA) biosynthesis. However, compared with the well-defined examples of sugar signaling in starch and anthocyanin synthesis, until recently relatively little was known about the role of signaling in regulating FA and lipid biosynthesis. Recent research progress shows that trehalose 6-phosphate and 2-oxoglutarate (2-OG) play direct signaling roles in the regulation of FA biosynthesis by modulating transcription factor stability and enzymatic activities involved in FA biosynthesis. Specifically, mechanistic links between sucrose non-fermenting−1–related protein kinase 1 (SnRK1)–mediated trehalose 6-phosphate (T6P) sensing and its regulation by phosphorylation of WRI1 stability, diacylglycerol acyltransferase 1 (DGAT1) enzyme activity, and of 2-OG–mediated relief of inhibition of acetyl-CoA carboxylase (ACCase) activity by protein PII are exemplified in detail in this review.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Progress in understanding and improving oil content and quality in seeds

The world’s population is projected to increase by two billion by 2050, resulting in food and energy insecurity. Oilseed crops have been identified as key to address these challenges: they produce and store lipids in the seeds as triacylglycerols that can serve as a source of food/feed, renewable fuels, and other industrially-relevant chemicals. Therefore, improving seed oil content and composition has generated immense interest. Research efforts aiming to unravel the regulatory pathways involved in fatty acid synthesis and to identify targets for metabolic engineering have made tremendous progress. This review provides a summary of the current knowledge of oil metabolism and discusses how photochemical activity and unconventional pathways can contribute to high carbon conversion efficiency in seeds. It also highlights the importance of 13 C-metabolic flux analysis as a tool to gain insights on the pathways that regulate oil biosynthesis in seeds. Finally, a list of key genes and regulators that have been recently targeted to enhance seed oil production are reviewed and additional possible targets in the metabolic pathways are proposed to achieve desirable oil content and quality.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Comprehensive characterization of extracellular vesicles produced by environmental (Neff) and clinical (T4) strains of Acanthamoeba castellanii

We conducted a comprehensive comparative analysis of extracellular vesicles (EVs) from two Acanthamoeba castellanii strains, Neff (environmental) and T4 (clinical). Morphological analysis via transmission electron microscopy revealed slightly larger Neff EVs (average = 194.5 nm) compared to more polydisperse T4 EVs (average = 168.4 nm). Nanoparticle tracking analysis (NTA) and dynamic light scattering validated these differences. Proteomic analysis of the EVs identified 1,352 proteins, with 1,107 common, 161 exclusive in Neff, and 84 exclusively in T4 EVs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping revealed distinct molecular functions and biological processes and notably, the T4 EVs enrichment in serine proteases, aligned with its pathogenicity. Lipidomic analysis revealed a prevalence of unsaturated lipid species in Neff EVs, particularly triacylglycerols, phosphatidylethanolamines (PEs), and phosphatidylserine, while T4 EVs were enriched in diacylglycerols and diacylglyceryl trimethylhomoserine, phosphatidylcholine and less unsaturated PEs, suggesting differences in lipid metabolism and membrane permeability. Metabolomic analysis indicated Neff EVs enrichment in glycerolipid metabolism, glycolysis, and nucleotide synthesis, while T4 EVs, methionine metabolism. Furthermore, RNA-seq of EVs revealed differential transcript between the strains, with Neff EVs enriched in transcripts related to gluconeogenesis and translation, suggesting gene regulation and metabolic shift, while in the T4 EVs transcripts were associated with signal transduction and protein kinase activity, indicating rapid responses to environmental changes. In this novel study, data integration highlighted the differences in enzyme profiles, metabolic processes, and potential origins of EVs in the two strains shedding light on the diversity and complexity of A. castellanii EVs and having implications for understanding host-pathogen interactions and developing targeted interventions for Acanthamoeba-related diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green alga Chromochloris zofingiensis

Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (–Fe). Cells grown in –Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Up-regulation of phosphoinositide metabolism in tobacco cells constitutively expressing the human type I inositol polyphosphate 5-phosphatase

To evaluate the impact of suppressing inositol 1,4,5-trisphosphate (InsP(3)) in plants, tobacco (Nicotiana tabacum) cells were transformed with the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme which specifically hydrolyzes InsP(3). The transgenic cell lines showed a 12- to 25-fold increase in InsP 5-ptase activity in vitro and a 60% to 80% reduction in basal InsP(3) compared with wild-type cells. Stimulation with Mas-7, a synthetic analog of the wasp venom peptide mastoparan, resulted in an approximately 2-fold increase in InsP(3) in both wild-type and transgenic cells. However, even with stimulation, InsP(3) levels in the transgenic cells did not reach wild-type basal values, suggesting that InsP(3) signaling is compromised. Analysis of whole-cell lipids indicated that phosphatidylinositol 4,5-bisphosphate (PtdInsP(2)), the lipid precursor of InsP(3), was greatly reduced in the transgenic cells. In vitro assays of enzymes involved in PtdInsP(2) metabolism showed that the activity of the PtdInsP(2)-hydrolyzing enzyme phospholipase C was not significantly altered in the transgenic cells. In contrast, the activity of the plasma membrane PtdInsP 5 kinase was increased by approximately 3-fold in the transgenic cells. In vivo labeling studies revealed a greater incorporation of (32)P into PtdInsP(2) in the transgenic cells compared with the wild type, indicating that the rate of PtdInsP(2) synthesis was increased. These studies show that the constitutive expression of the human type I InsP 5-ptase in tobacco cells leads to an up-regulation of the phosphoinositide pathway and highlight the importance of PtdInsP(2) synthesis as a regulatory step in this system.

NASA Discipline Cell Biology↗
DOE OSTI2024

Increased triacylglycerol production in Rhodococcus opacus by overexpressing transcriptional regulators

Lignocellulosic biomass is currently underutilized, but it offers promise as a resource for the generation of commercial end-products, such as biofuels, detergents, and other oleochemicals. Rhodococcus opacus PD630 is an oleaginous, Gram-positive bacterium with an exceptional ability to utilize recalcitrant aromatic lignin breakdown products to produce lipid molecules such as triacylglycerols (TAGs), which are an important biofuel precursor. Lipid carbon storage molecules accumulate only under growth-limiting low nitrogen conditions, representing a significant challenge toward using bacterial biorefineries for fuel precursor production. In this work, we screened overexpression of 27 native transcriptional regulators for their abilities to improve lipid accumulation under nitrogen-rich conditions, resulting in three strains that accumulate increased lipids, unconstrained by nitrogen availability when grown in phenol or glucose. Transcriptomic analyses revealed that the best strain (#13) enhanced FA production via activation of the β-ketoadipate pathway. Gene deletion experiments confirm that lipid accumulation in nitrogen-replete conditions requires reprogramming of phenylalanine metabolism. By generating mutants decoupling carbon storage from low nitrogen environments, we move closer toward optimizing R. opacus for efficient bioproduction on lignocellulosic biomass.

09 BIOMASS FUELS↗
DOE OSTI2024

High-throughput chemical imaging for optimizing biofuel synthesis using synthetic biology (Final Technical Report)

Fatty acids can be produced biosynthetically in microbes and these compounds can serve as precursors to biodiesels and other high value oleochemicals. However, progress on engineering fatty acid biosynthesis, and biofuel synthesis more generally, has been hindered by current quantification methods that are either indirect or not amenable to high-throughput or single-cell resolution screening. In this project, we assembled an interdisciplinary team with complimentary expertise in synthetic biology and microscopy, metabolic engineering, and chemical imaging to address these challenges. We used chemical imaging to directly measure lipid biosynthesis in Escherichia coli engineered to produce fatty acids, obtaining detailed single-cell resolution measurements. We deployed stimulated Raman scattering (SRS) microscopy in concert with multiplexed genome engineering and gene circuit design strategies from synthetic biology to optimize production of fatty acids. These results provided novel insight into cell-to-cell heterogeneity present in biofuel production strains. In addition, we introduced new chemical imaging methods which are label-free and do not require fluorescent reporters. These efforts were complemented by other studied developing foundational tools for regulation and control, which offer excellent potential for advancing researchers’ ability to rapidly design, build, and test strains for enhanced biofuel synthesis.

09 BIOMASS FUELS↗
DOE OSTI2025

The key role of the ferroptosis mechanism in neurological diseases and prospects for targeted therapy

Neurological disorders represent a major global health concern owing to their intricate pathological processes. Ferroptosis, defined as a form of cell death that is reliant on iron, has been closely linked to various neurological conditions. The fundamental process underlying ferroptosis is defined by the excessive buildup of iron ions, which initiates lipid peroxidation processes leading to cellular demise. Neurons, as highly metabolically active cells, are susceptible to oxidative stress, and imbalances in iron metabolism can directly initiate the ferroptosis process. In neurodegenerative disorders like Alzheimer’s disease and Parkinson’s disease, ferroptosis driven by iron accumulation represents a fundamental pathological connection. Although the connection between ferroptosis and neurological diseases is clear, clinical application still faces challenges, such as precise regulation of iron metabolism, development of specific drugs, and assessment of efficacy. The limited comprehension of the ferroptosis mechanism hinders the development of personalized treatment approaches. Consequently, subsequent investigations must tackle these obstacles to facilitate the clinical application of ferroptosis-associated therapies in neurological disorders. This article provides a comprehensive overview of the most recent advancements regarding the underlying mechanisms of ferroptosis. Subsequently, the study investigates the mechanistic contributions of ferroptosis within the nervous system. In conclusion, we evaluate and deliberate on targeted therapeutic strategies associated with ferroptosis and neurological disorders.

Xie, Chenyu↗
DOE OSTI2025

Nitrogen limitation causes a seismic shift in redox state and phosphorylation of proteins implicated in carbon flux and lipidome remodeling in Rhodotorula toruloides

Background: Oleaginous yeast are prodigious producers of oleochemicals, offering alternative and secure sources for applications in foodstuff, skincare, biofuels, and bioplastics. Nitrogen starvation is the primary strategy used to induce oil accumulation in oleaginous yeast as part of a global stress response. While research has demonstrated that post-translational modifications (PTMs), including phosphorylation and protein cysteine thiol oxidation (redox PTMs), are involved in signaling pathways that regulate stress responses in metazoa and algae, their role in oleaginous yeast remain understudied and unexplored. Results: Towards linking the yeast oleaginous phenotype to protein function, we integrated lipidomics, redox proteomics, and phosphoproteomics to investigate Rhodotorula toruloides under nitrogen-rich and starved conditions over time. Our lipidomics results unearthed interactions involving sphingolipids and cardiolipins with ER stress and mitophagy. Our redox and phosphoproteomics data highlighted the roles of the AMPK, TOR, and calcium signaling pathways in regulation of lipogenesis, autophagy, and oxidative stress response. As a first, we also demonstrated that lipogenic enzymes including fatty acid synthase are modified as a consequence of shifts in cellular redox states due to nutrient availability. Conclusions: We conclude that lipid accumulation is largely a consequence of carbon rerouting and autophagy governed by changes to PTMs, and not increases in the abundance of enzymes involved in central carbon metabolism and fatty acid biosynthesis. Our systems-level approach sets the stage for acquiring multidimensional data sets for protein structural modeling and predicting the functional relevance of PTMs using Artificial Intelligence/Machine Learning (AI/ML). Coupled to those bioinformatics approaches, the putative PTM switches that we delineate will enable advanced metabolic engineering strategies to decouple lipid accumulation from nitrogen limitation.

Lipid Signalling↗
DOE OSTI2026

Novel Cell-Type-Specific Drought-Responsive Proteins in Root Tips of Field-Grown Perennial Switchgrass

The root-tip region of plants, including the root cap, forms the most basal terminal of the root and exhibits a high degree of cellular complexity in terms of morphology, cytological function, and interaction with environmental cues in the soil. Cells in this region follow a developmental trajectory, transitioning from stem cells to meristematic cells, and ultimately to fully differentiated cell types. However, our understanding of root-tip cell-type specific proteomic responses to abiotic stresses, such as drought, particularly under field conditions, remains limited. This study aimed to identify spatially resolved, cell type-specific proteomes in switchgrass (Panicum virgatum) root tips under drought stress. Root tips were collected from seven-year-old, field-grown switchgrass ‘Alamo’ plants excavated under both well-watered and long-term drought conditions. Cell type-specific proteins were identified using laser capture microdissection (LCM) coupled with nanoPOTS (Nanodroplet Processing in One Pot for Trace Samples) and nano-LC-MS proteomics analysis. Five distinct cell types were targeted: (1) cells in the quiescent center and stem cell niche (QuC), (2) protodermal epidermal cells (PEC) in the meristematic zone, (3) epidermal cells in the transition and elongation zones above the root cap (Epi), (4) peripheral root cap cells (PRC), forming 2–3 layers below the PEC and 1–2 layers above the root border cells, and (5) columella root cap cells (Col) comprising of the columella initials and a single underlying layer of cells undergoing active growth. Principal component analysis (PCA) revealed clear separation among the five targeted cell types, confirming distinct proteomic profiles. Proteins predominantly enriched in each cell type were linked to distinct cellular functions, with QuC cells showing involvement in chromosomal behavior, DNA replication, and mitosis—key processes for stem cell niche regulation. Drought stress resulted in alterations of proteostasis, as evidenced by significant decreases in ribosomal proteins and increases in protein synthesis inhibitors. Moreover, drought stress induced unique cell-type–specific proteins involved in phytohormone biosynthesis and signaling pathways, including auxin, cytokinin, and jasmonic acid. In particular, QuC cells were more highly enriched in proteins associated with DNA repair and mitotic processes. Metabolic pathways related to amino acids, carbohydrates, and lipids were differentially affected in a cell-type–dependent manner, whereas general stress-responsive proteins exhibited consistent changes across all five cell types. Overall, this study provides unique spatially resolved, cell-type-specific proteomic profiles in root tips, representing a significant advancement in our understanding of the cellular mechanisms underlying plant responses to drought stress in natural field conditions.

perennial grass↗
DOE OSTI2025

Knocking out the carboxyltransferase interactor 1 (CTI1) in Chlamydomonas boosted oil content by fivefold without affecting cell growth

Summary The first step in chloroplast de novo fatty acid synthesis is catalysed by acetyl‐CoA carboxylase (ACCase). As the rate‐limiting step for this pathway, ACCase is subject to both positive and negative regulation. In this study, we identify a Chlamydomonas homologue of the plant carboxyltransferase interactor 1 (CrCTI1) and show that this protein interacts with the Chlamydomonas α‐carboxyltransferase (Crα‐CT) subunit of the ACCase by yeast two‐hybrid protein–protein interaction assay. Three independent CRISPR‐Cas9 mediated knockout mutants for CrCTI1 each produced an ‘enhanced oil’ phenotype, accumulating 25% more total fatty acids and storing up to fivefold more triacylglycerols (TAGs) in lipid droplets. The TAG phenotype of the crcti1 mutants was not influenced by light but was affected by trophic growth conditions. By growing cells under heterotrophic conditions, we observed a crucial function of CrCTI1 in balancing lipid accumulation and cell growth. Mutating a previously mapped in vivo phosphorylation site (CrCTI1 Ser108 to either Ala or to Asp), did not affect the interaction with Crα‐CT. However, mutating all six predicted phosphorylation sites within Crα‐CT to create a phosphomimetic mutant reduced this pairwise interaction significantly. Comparative proteomic analyses of the crcti1 mutants and WT suggested a role for CrCTI1 in regulating carbon flux by coordinating carbon metabolism, antioxidant and fatty acid β‐oxidation pathways, to enable cells to adapt to carbon availability. Taken together, this study identifies CrCTI1 as a negative regulator of fatty acid synthesis in algae and provides a new molecular brick for the genetic engineering of microalgae for biotechnology purposes.

Li, Zhongze [Aix‐Marseille Université, CEA, CNRS, ↗
DOE OSTI2023

Genomics of turions from the Greater Duckweed reveal its pathways for dormancy and re‐emergence strategy

Summary Over 15 families of aquatic plants are known to use a strategy of developmental switching upon environmental stress to produce dormant propagules called turions. However, few molecular details for turion biology have been elucidated due to the difficulties in isolating high‐quality nucleic acids from this tissue. We successfully developed a new protocol to isolate high‐quality transcripts and carried out RNA‐seq analysis of mature turions from the Greater Duckweed Spirodela polyrhiza . Comparison of turion transcriptomes to that of fronds, the actively growing leaf‐like tissue, were carried out. Bioinformatic analysis of high confidence, differentially expressed transcripts between frond and mature turion tissues revealed major pathways related to stress tolerance, starch and lipid metabolism, and dormancy that are mobilized to reprogram frond meristems for turion differentiation. We identified the key genes that are likely to drive starch and lipid accumulation during turion formation, as well as those in pathways for starch and lipid utilization upon turion germination. Comparison of genome‐wide cytosine methylation levels also revealed evidence for epigenetic changes in the formation of turion tissues. Similarities between turions and seeds provide evidence that key regulators for seed maturation and germination were retooled for their function in turion biology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Endurance exercise elicits temporal and sexual dimorphic multi-omics remodeling of liver metabolism revealed by MoTrPAC

The mechanisms by which exercise modulate liver metabolism, a central regulator of systemic metabolism, are poorly understood. Leveraging data from MoTrPAC, we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omic approaches. Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) complexes (at the protein level), while male livers showed an increase in acetylation of OXPHOS, TCA cycle, and fatty acid oxidation enzymes. Exercise also enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise. Male rats had higher fecal cholesterol and cholic acid levels, indicating a sex-specific mechanism of lipid excretion with exercise. Moreover, 8 weeks of training reduced markers related to hepatic stellate cell activation and fibrosis in both sexes. This study highlights the sexual dimorphic and temporal molecular signatures by which exercise modulates liver metabolism to provide hepatoprotective effects.

Kelty, Taylor↗
DOE OSTI2025

An Algal Nutrient‐Replete, Optimized Medium for Fast Growth and High Triacylglycerol Accumulation

Microalgae are promising sources to sustainably meet the global needs for energy and products. Algae grow under different trophic conditions, where nutritional status regulates biosynthetic pathways, energy production, and growth. The green alga Chromochloris zofingiensis has strong economic potential because it co-produces biofuel precursors and the high-value antioxidant astaxanthin while accumulating biomass when grown mixotrophically. As an emerging reference alga for photosynthesis, metabolism, and bioproduction, C. zofingiensis needs a defined, optimized medium to standardize experiments during fast growth for batch cultivation. Because the interplay of glucose treatment (+Glc) and mineral deficiency influences photosynthesis, growth, and the production of lipids and astaxanthin, we designed a replete nutrient medium tailored to the C. zofingiensis cellular ionome. We combined inductively coupled plasma mass spectrometry (ICP-MS) and +Glc growth curves to determine a medium that is nutrient replete for at least 5 days of +Glc logarithmic growth. We found that there are high nutritional needs for phosphorus and sulfur during mixotrophy. Iron was the only element measured for which the cellular concentration correlated with exogenous concentration and was iteratively adjusted until the cellular ionome was consistent through the logarithmic growth phase. This Chromochloris-Optimized Ratio of Elements (CORE) medium supports fast growth and high biomass and lipid accumulation without causing excess nutrient toxicity. This defined, nutrient-replete standard is important for future C. zofingiensis investigations and can be adapted for other species to support high biomass for batch cultivation. The method used to develop CORE medium shows how ionomics informs replicable media design and may be applied in industrial settings to inform cost-effective biofuel production.

Jeffers, Tim L. [University of California, Berkele↗
DOE OSTI2024

The phycosphere and its role in algal biofuel production

Oleaginous microalgae have become a focus for large-scale biofuel production due to their ability to accumulate large quantities of lipids. However, production is currently limited by cost and predation. At present, algal biofuel cultivation is optimized through starvation, supplementing media with nutrients, or genetic engineering; these methods can often be costly with little to no increase in lipid production or the culture’s defense. Investigating the phycosphere of algal-bacterial interactions may overcome these current barriers to large-scale production. The phycosphere of algal-bacterial interactions have formed over millions of years through mutualistic and symbiotic relationships and can provide a more direct source of nutrients compared to adding the nutrients in bulk. The most promising of these interactions include the production of phytohormones and quorum signaling compounds that alter the behaviors of the consortia. Phytohormones can improve algal growth rates, lipid production, and stress resistance. Quorum signaling could create consortia capable of warding off invaders—such as rotifers—while self-regulating and altering behavior based on population density. Mechanisms within the algal phycosphere present many opportunities for the development of novel engineering strategies to further improve algal lipid production and operational costs. This review outlines previous preliminary phycosphere research as well as posing possible opportunities to be pursued in future biofuel production.

09 BIOMASS FUELS↗