Accumulation of ammonium owing to the metabolic imbalance of carbon and nitrogen might inhibit the central metabolism in Methylomonas sp. ZR1

Guo, W.; He, R.; Zhao, Y.; Li, D.

doi:10.1101/2020.01.22.916338

Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.01.22.916338

Accumulation of ammonium owing to the metabolic imbalance of carbon and nitrogen might inhibit the central metabolism in Methylomonas sp. ZR1

Guo, W.·He, R.·Zhao, Y.·Li, D.

View original source ↗Export metadata ↓

Abstract

The metabolic intermediates of nitrogen source have been proved to have multiple functions on the metabolism of mehthanotrophs. In this study, accumulation and assimilation mechanism of the nitrate metabolic intermediate ammonium in the fast growing Methylomonas sp. ZR1 was analyzed. Although, nitrate salt was the best nitrogen source supporting the growth of ZR1, its metabolic intermediate ammonium would accumulate and inhibit ZR1. Kinetic studies indicated that accumulation of NH4+ was deduced from the imbalance of nitrogen and carbon metabolism. Compensation of carbon skeleton -keto-glutaramate could effectively relieve the inhibition of NH4+ to ZR1, which further approved the assumption. qPCR analysis indicated a third ammonium assimilation pathway Glycine synthesis system may function in ZR1 under high ammonium tension. In the presence of ammonium, ZR1 might employ two strategies to relieve the ammonium stress, one was assimilating the excess ammonium, and another one was cutting off the nitrogen reduction reactions. Investigation of the nitrogen metabolism and its influence to the carbon metabolism is meaningful to systematically understand and control the C1 feedstock bioconversion process in methanotrophs. ImportanceThe nitrogen metabolism in methanotrophs has long been concerned. However, there are lots of research problems yet to be solved. In this study, the accumulation and assimilation mechanism of the nitrogen metabolic intermediate ammonium in the fast growing Methylomonas sp. ZR1 was analyzed. Owing to the imbalance metabolism of carbon and nitrogen source, ammonium would accumulate to high concentrations to inhibit cell growth. Compensation of carbon skeleton was an effective strategy to relieve the inhibition of NH4+. A third ammonium assimilation pathway related genes were proved actively expressing in ZR1 when it confronted with high ammonium tension. When confronted with ammonium tension, ZR1 might employ different strategies to relieve the ammonium stress according to the edible carbon source. Revealing the endogenous ammonium accumulation mechanism and its metabolic adjustment effect on the central metabolism of methanotrophs, was meaningful to reveal the complex coordination metabolic mechanism of nitrogen and carbon in methanotrophs.

Explore related subjects

physiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Guo, W., He, R., Zhao, Y., Li, D.. 2020-01-23. Accumulation of ammonium owing to the metabolic imbalance of carbon and nitrogen might inhibit the central metabolism in Methylomonas sp. ZR1. https://doi.org/10.1101/2020.01.22.916338

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Epigenetic Rescue of Disuse Muscle Atrophy by Histone Deacetylase Inhibitor Trichostatin A

Mechanical unloading rapidly induces skeletal muscle atrophy and functional deterioration, yet how the loss of mechanical input influences nuclear architecture, chromatin organization, and associated transcriptional programs remains poorly understood. Here, we investigated whether pharmacological inhibition of histone deacetylases (HDACs) using Trichostatin A (TSA) could attenuate the consequences of continued mechanical unloading in a murine hindlimb suspension model. Following 14 days of unloading, mice exhibited impaired locomotor activity, altered muscle architecture, and widespread transcriptional reprogramming characterized by increased expression of atrophy associated genes, inflammatory mediators, and extracellular matrix remodeling pathways, alongside suppression of mitochondrial metabolic programs. Super resolution imaging further revealed irregular Lamin A/C organization and disruption of discrete H3K9me3 associated heterochromatin foci. Systemic TSA treatment significantly attenuated the decline in locomotor activity, accompanied by trends toward reduced body weight loss, and preservation of muscle morphology. Transcriptomic analysis demonstrated a substantial shift toward the baseline expression profile, with high-dose TSA attenuating FOXO associated catabolic programs, inflammatory, and extracellular matrix-related signatures, while enhancing mitochondrial oxidative phosphorylation pathways. Quantitative gene level and pathway analyses further revealed dose dependent and selective reversal of unloading associated transcriptional changes. Notably, TSA treatment also partially preserved nuclear lamina organization and the focal distribution of H3K9me3 associated heterochromatin. Despite these muscle specific benefits, TSA did not prevent trabecular bone loss over the 14-day unloading period, although several muscle-expressed genes potentially involved in muscle to bone communication were altered by treatment. Together, these findings demonstrate that HDAC inhibition counteracts multiple functional and molecular consequences of skeletal muscle unloading and is associated with partial preservation of nuclear and heterochromatin organization. This study supports a link between mechanical unloading, nuclear architectural remodeling, and HDAC sensitive transcriptional regulation, providing a foundation for epigenetic strategies to counter disuse induced muscle deterioration.

physiology↗

bioRxiv2026

Residual Hearing Loss After Chronic Cochlear Implantation in Guinea Pigs is Primarily Conductive

It is desirous to preserve residual low-frequency hearing in cochlear implant recipients, as dual stimulation using electrical and acoustic signals results in superior speech-in-noise processing and musicality. However, cochlear implant recipients commonly lose their residual acoustic hearing gradually following surgical placement of the array. The governing mechanism is not understood and is likely due to multiple factors including surgical trauma, inflammation, and the foreign body induced immune response to the array, including formation of intracochlear fibrosis. Normal mechanical function of the cochlea is expected to underpin residual hearing but has not been directly studied. This function includes efficient transmission of sound to the cochlea via the middle ear, sound propagation via the basilar membrane travelling wave, mechanical tuning characteristics, and the non-linear cochlear amplification of responses to low-frequency stimulation. Here, we examined these features in cochleae and middle ears of unimplanted, acutely and chronically implanted guinea pigs using our minimally invasive preparation and optical coherence tomography vibrometry. We observed that mechanical tuning and amplification is not significantly altered by either acute or chronic implant. However, the response threshold was raised and proportional to middle ear responses. Additionally, the organ of Corti phase, and its sound intensity dependent changes, are unaltered by CI. Finally, a cluster analysis revealed sensitivity loss in chronically implanted animals is caused by middle ear dysfunction. Hence, in the guinea pig model, the dominant etiology of residual hearing loss is conductive. More research is required to establish whether residual hearing loss in humans similarly shares conductive elements.

physiology↗

bioRxiv2026

Satellite cell glucocorticoid receptor restrains myogenic commitment without mediating the effects of therapeutic glucocorticoids on muscle repair

Glucocorticoids (GCs) exert profound effects on skeletal muscle, but the contribution of satellite cell (SatC) glucocorticoid receptor (GR) signaling to muscle regeneration remains poorly understood. Here, we investigated the role of GR in SatC homeostasis and assessed whether SatC GR mediates the effects of therapeutic GCs on muscle repair. Conditional deletion of GR in SatC reduced the number of PAX7-positive cells during regeneration in young mice, but did not substantially impair muscle repair in either young or aged animals. Transcriptomic and chromatin profiling revealed that GR occupies genes involved in stem cell fate and developmental signaling, with extensive GR binding already established in quiescent SatC. GR-deficient quiescent SatC showed reduced expression of Yap1, Runx1 and Foxo1, together with increased Myog expression. Similarly, GR silencing in human myoblasts induced early myogenic differentiation markers without affecting proliferation, supporting a conserved role for GR in restraining myogenic commitment. We next examined the effects of two therapeutic GCs on muscle regeneration. Chronic prednisone treatment altered the transcriptional landscape of regenerating muscle in an age-dependent manner, without substantially affecting histological repair. In contrast, dexamethasone administration during the early inflammatory phase delayed regeneration, with persistent necrosis and increased collagen deposition. These effects were comparable in control and SatC-specific GR-deficient mice, indicating that they do not require GR in SatC. Together, these findings identify GR as a regulator of the quiescent, undifferentiated state of SatC, while showing that the effects of therapeutic GCs on muscle repair are largely independent of SatC GR. They further highlight the importance of treatment regimen and physiological context in determining the effects of GCs on skeletal muscle regeneration.

physiology↗