Comprehensive analysis of protein acetylation and glucose metabolism inmouse brains infected with rabies virus

Rabies, caused by rabies virus (RABV), is a widespread zoonosis that is nearly 100% fatal. Alteration of the metabolic environment affects viral replication and the immune response during viral infection. In this study, glucose uptake was increased in mouse brains at the late stage of infection with different RABV strains (lab-attenuated CVS strain and wild-type DRV strain). To illustrate the mechanism underlying glucose metabolism alteration, comprehensive analysis of lysine acetylation and target analysis of energy metabolites in mouse brains infected with CVS and DRV strains were performed. A total of 156 acetylated sites and 115 acetylated proteins were identified as significantly different during RABV infection. Compared to CVS- and mock-infected mice, the lysine acetylation levels of glycolysis and tricarboxylic acid (TCA) cycle enzymes were decreased, and enzyme activity was upregulated in DRV-infected mouse brains. Metabolomic analysis revealed that high levels of oxaloacetate (OAA) in RABV-infected mouse brains. Specifically, the OAA level in CVS-infected mouse brains was higher than that in DRV-infected mouse brains, which contributed to the enhancement of the metabolic rate at the substrate level. Finally, we confirmed that OAA could reduce excessive neuroinflammation in CVS-infected mouse brains by inhibiting JNK and P38 phosphorylation. Taken together, this study provides fresh insight into the different strategies the host adapts to regulate glucose metabolism for energy requirements after different RABV strain infection and suggest that OAA treatment could be a potential strategy to prevent neural damage during RABV infection. IMPORTANCE Both viral replication and the host immune response are highly energy-dependent. It is important to understand how the rabies virus affects energy metabolism in the brain. Glucose is the direct energy source for cell metabolism. Previous studies have revealed that there is some association between acetylation and metabolic processes. In this study, comprehensive protein acetylation and glucose metabolism analysis were conducted to compare glucose metabolism in mouse brains infected with different RABV strains. Our study demonstrates that the regulation of enzyme activity by acetylation and OAA accumulation at the substrate level are two strategies for the host to respond to the energy requirements after RABV infection. Our study also indicates the potential role OAA could play in neuronal protection by suppressing excessive neuroinflammation.

Microbial fermentation of polyethylene terephthalate (PET) plastic waste for the production of chemicals and electricity

Ideonella sakaiensis (I. sakaiensis) can grow on polyethylene terephthalate (PET) as the sole carbon and energy source. Previous work has shown that conversion of the hydrolysis products terephthalic acid (TPA) and ethylene glycol (EG) under aerobic conditions released carbon dioxide and water while yielding adenosine triphosphate (ATP) through oxidative phosphorylation. This study demonstrates that under anaerobic conditions I. sakaiensis ferments PET to the feedstock chemicals acetate and ethanol while co-producing ATP by substrate-level phosphorylation. In addition to PET, maltose, EG, and ethanol can also serve as fermenting substrates. Co-culturing of I. sakaiensis with electrogenic Geobacter sulfurreducens produced electricity from PET or EG. This newly identified plastic fermentation process by I. sakaiensis provides a novel biosynthetic route to produce high-value chemicals and electricity from plastic waste streams.

Aerobic glycolysis in cancer cells supplies ATP while preventing excess metabolic thermogenesis

A general feature of cancer metabolism is ATP regeneration via substrate-level phosphorylation even under normoxic conditions (aerobic glycolysis). However, it is unclear why cancer cells prefer the inefficient aerobic glycolysis over the highly efficient process of oxidative phosphorylation for ATP regeneration. Here, we show that a beneficial aspect of aerobic glycolysis is that it reduces metabolic heat generation during ATP regeneration. 13C-metabolic flux analysis of 12 cultured cancer cell lines and in silico metabolic simulation revealed that metabolic heat production during ATP regeneration via aerobic glycolysis was considerably lesser than that produced via oxidative phosphorylation. The dependency on aerobic glycolysis was partly alleviated upon culturing under low temperatures. In conclusion, thermogenesis is required for maintaining thermal homeostasis and can govern aerobic glycolysis in cancer cells.

Biosynthesis and Transport of Nucleotide Sugars for Plant Hemicellulose

Hemicellulose is entangled with cellulose through hydrogen bonds and meanwhile acts as a bridge for the deposition of lignin monomer in the secondary wall. Therefore, hemicellulose plays a vital role in the utilization of cell wall biomass. Many advances in hemicellulose research have recently been made, and a large number of genes and their functions have been identified and verified. However, due to the diversity and complexity of hemicellulose, the biosynthesis and regulatory mechanisms are yet unknown. In this review, we summarized the types of plant hemicellulose, hemicellulose-specific nucleotide sugar substrates, key transporters, and biosynthesis pathways. This review will contribute to a better understanding of substrate-level regulation of hemicellulose synthesis.

A prebiotic basis for ATP as the universal energy currency

ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires six phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP-equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleotide triphosphates, remains a mystery. Here we show that the deep conservation of ATP reflects its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate, which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that acetyl phosphate can phosphorylate ADP to ATP at nearly 20 % yield in water in the presence of Fe3+ ions. We then show that Fe3+ and acetyl phosphate are surprisingly favoured: a panel of other prebiotically relevant ions and minerals did not catalyze ADP phosphorylation; nor did a number of other potentially prebiotic phosphorylating agents. Only carbamoyl phosphate showed some modest phosphorylating activity. Critically, we show that acetyl phosphate does not phosphorylate other nucleotide diphosphates or free pyrophosphate in water. The phosphorylation of ADP monomers seems to be favoured by the interaction between the N6 amino group on the adenine ring with Fe3+ coupled to acetyl phosphate. Our findings suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

CK2 Regulation: Perspectives in 2021

The protein kinase CK2 (CK2) family encompasses a small number of acidophilic serine/threonine kinases that phosphorylate substrates involved in numerous biological processes including apoptosis, cell proliferation, and the DNA damage response. CK2 has also been implicated in many human malignancies and other disorders including Alzheimer′s and Parkinson’s diseases, and COVID-19. Interestingly, no single mechanism describes how CK2 is regulated, including activation by external proteins or domains, phosphorylation, or dimerization. Furthermore, the kinase has an elongated activation loop that locks the kinase into an active conformation, leading CK2 to be labelled a constitutively active kinase. This presents an interesting paradox that remains unanswered: how can a constitutively active kinase regulate biological processes that require careful control? Here, we highlight a selection of studies where CK2 activity is regulated at the substrate level, and discuss them based on the regulatory mechanism. Overall, this review describes numerous biological processes where CK2 activity is regulated, highlighting how a constitutively active kinase can still control numerous cellular activities. It is also evident that more research is required to fully elucidate the mechanisms that regulate CK2 and what causes aberrant CK2 signaling in disease.

Visual displays in a nocturnal rhacophorid frog (Buergeria japonica)

We report a visual display, leg-stretching, in the nocturnal Ryukyu Kajika frog (Buergeria japonica) on Iriomote Island in southern Okinawa, Japan. This visual display is produced by males before, during, or after a vocalization and involves the extension of one or both hindlimbs outwards at substrate level. Leg-stretches in this species are performed during male-male agonistic interactions in choruses, and almost exclusively in concert with aggressive vocalizations. These observations are one of the first reports of visual displays for the Rhacophoridae family and provide insights into why visual displays evolve in frogs, especially in nocturnal species. We discuss our observations in the context of underlying mechanisms and selective pressures driving the evolution of anuran visual displays.

A Theoretical Model of Mitochondrial ATP Synthase Deficiencies. The Role of Mitochondrial Carriers

The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-c-oxidase, preventing yeast growth on oxidative substrates. The overexpression of the mitochondrial oxodicarboxylate carrier (Odc1p) was able to rescue the growth on the oxidative substrate by increasing the substrate-level phosphorylation of ADP coupled to the conversion of α-ketoglutarate (AKG) into succinate with an increase in Complex IV activity. Previous studies showed that equivalent point mutations in ATP synthase behave similarly and can be rescued by Odc1p overexpression and/or the uncoupling of OXPHOS from ATP synthesis. In order to better understand the mechanism of the ATP synthase mutation bypass, we developed a core model of mitochondrial metabolism based on AKG as a respiratory substrate. We describe the different possible metabolite outputs and the ATP/O ratio values as a function of ATP synthase inhibition.

Estimasi Biomassa dan Simpanan Karbon pada Vegetasi Lamun di Perairan Pantai Jepara

Peningkatan emisi karbon yang berasal dari berbagai aktivitas manusisa dapat mengakibatkan terjadinya pemanasan global. Salah satu upaya untuk mengurangi emisi gas karbon adalah dengan memanfaatkan vegetasi pesisir seperti lamun yang dikenal dengan istilah blue carbon. Ekosistem lamun merupakan salah satu ekosistem pesisir yang dapat menyerap dan menyimpan karbon dalam jumlah yang besar dan dalam waktu yang lama. Penelitian ini bertujuan untuk mengetahui kerapatan, tutupan lamun, nilai biomassa dan simpanan karbon pada lamun di Pantai Blebak dan Pantai Prawean, Kabupaten Jepara. Metode survei dan penentuan lokasi dipilih dengan menggunakan metode purposive sampling, sedangkan metode pengambilan data lamun melalui metode line transect quadrant dengan ukuran 50x50 cm yang mengacu pada metode LIPI 2017. Perhitungan kandungan karbon menggunakan metode Loss On Ignition (LOI). Hasil kerapatan lamun total pada Pantai Prawean yaitu sebesar 221,45 ind/m2 dan nilai tutupan total lamun sebesar 45,98%. Kerapatan lamun total pada Pantai Blebak yaitu sebesar 160 ind/m2 dan nilai tutupan total lamun sebesar 41,67%. Nilai biomassa bawah substrat dan atas substrat pada Pantai Prawean (726,25 gbk/m2 dan 500,50 gbk/m2) menunjukkan nilai yang lebih besar dibandingkan nilai biomassa bawah substrat dan atas substrat pada Pantai Blebak (606,50 gbk/m2 dan 370,75 gbk/m2). Total kandungan karbon pada Pantai Prawean adalah 464,10 gC/m2 sedangkan pada Pantai Blebak adalah 357,79 gC/m2. Hasil perhitungan total stok karbon yang didapatkan menunjukkan bahwa Pantai Prawean memiliki nilai biomassa dan total stok karbon yang lebih tinggi daripada Pantai Blebak. Human activities lead to the increasing of carbon emission, which caused global warming. Seagrass and other coastal vegetation are being used to reduce carbon emission. This is known as blue carbon. The seagrass ecosystem is one of coastal ecosystem that can absorb and stock high amount of carbon in a short period of time. This study was done to determine the density, seagrass coverage, biomass, and carbon stock within the seagrass in Prawean and Blebak Beach, Jepara. Survey method and location determination method were done with purposive sampling method. Whereas, the seagrass data was collected by Line Transect Quadrant method 50x50 cm based on LIPI’s 2017 method. Loss on Ignition method was used to measure the carbon’s content. The density of total seagrass in Prawean beach is 221,45 ind/m2 and the total percentage of seagrass coverage is 45,98%. Total density of seagrass in Blebak Beach is 160 ind/m2 with a coverage percentage of 41,67%. The biomass below the substrate level and above the substrate level in Prawean Beach (726,25 gbk/m2 and 500,50 gbk/m2) showed a bigger amount than the amount of biomass in Blebak Beach (606,50 gbk/m2 and 370,75 gbk/m2). Total amount of carbon in Prawean is 464,10 gC/m2 meanwhile in Blebak, the amount of carbon is 357,79 gC/m2. The results of the total carbon stock obtained indicate that Prawean Beach has higher biomass and total carbon stock values than Blebak Beach.