SARS-Cov2 seasonality and adaptation are driven by solar activity. DOI Creative Commons
Octavio Gonzalez-Lugo

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 22, 2023

Abstract Since its isolation, SARS-Cov2 showed a high mutation rate hindering the ability to properly characterize it. Also as consequence of size, traditional sequence analysis methods are computationally constrained. Nonetheless, machine learning technologies and particularly deep offer viable scalable solution analysis. Applying variational autoencoders (VAEs), special kind neural network used for unsupervised learning, custom genomic representations cluster genomes by similarity. The resulting learned representation sorts sunshine duration (SD) change (SDRC) other solar-derived features. transition between clusters is characterized changes in viral genome size. Different deletions can be found throughout genome. Deletions might behave an internal clock inside Or adaptation mechanism seasonal variations solar radiation. As follows SDRC COVID-19 cases could also follow same pattern. However, spherical geometry our planet adds confounding variable Spherical correction dynamic fractional differentiation SD synchronizes into single period. This results general coordinate system that shows seasonality disease allows us analyze impact environmental Atmospheric affect radiation such ozone column cloudiness gradients correlation with cases. Analyzing composition (amount each specific nucleotide) time series displays attractor-like behavior under different scales. Oscillations explain efficacy antiviral treatments through pandemic. To further expand prediction capability model set features added targets supervised task. Allowing correlate composition. Genome sorting obtained two-dimensional appears only one dimension encodes temporal variable. show interaction host or particular tissue virus. VAE modified fit predator-prey using observations model. Retrieved dynamics transitory phase similar incubation time. characterization needed accurately interpret those results. Under system, mutations adaptations regular deterministic If result means copy codon usage bias(CUB) it likely expression compositionally genes. Selection highly transcripts isolation genes whose dysregulation matches some symptoms reported post-acute sequelae long Covid. Also, regulate circadian rhythm expressed at periods prevalence. Copying optimizing towards host's CUB will increase probability virus significant fragment protein leading autoimmunity. Dysregulation solar-based regulation variability random-like post acute phase. Further development techniques help better understand pathogenic organisms.

Language: Английский

Mitochondria at the crossroads of health and disease DOI Creative Commons
Anu Suomalainen, Jodi Nunnari

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2601 - 2627

Published: May 1, 2024

Mitochondria reside at the crossroads of catabolic and anabolic metabolism—the essence life. How their structure function are dynamically tuned in response to tissue-specific needs for energy, growth repair, renewal is being increasingly understood. respond intrinsic extrinsic stresses can alter cell organismal by inducing metabolic signaling within cells distal tissues. Here, we review how centrality mitochondrial functions manifests health a broad spectrum diseases aging.

Language: Английский

Citations

105
WBSCR16 is essential for mitochondrial 16S rRNA processing in mammals DOI Creative Commons
Shengjie Zhang, Zi Dong, Feng Yang

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(3)

Published: Jan. 24, 2025

Abstract Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/-mice cells, both of which exhibited dramatic changes. Subsequently, WBSCR16 was identified as a rRNA-binding protein essential for cleavage rRNA-mt-tRNALeu, facilitating ribosome assembly. Additionally, recruited RNase P subunit MRPP3 to nascent assisted this specific cleavage. Furthermore, evidence showed Wbscr16 ablation promotes wasting via lipid preference brown adipose tissue, leading excess expenditure resistance obesity. In contrast, overexpression upregulated induced glucose utilization transgenic mouse models cultured cells. These findings suggest plays mammals, is key balance metabolism.

Language: Английский

Citations

1
Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression DOI
Nicholas J. Kramer, Gyan Prakash, R. Stefan Isaac

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(11), P. 1575 - 1589

Published: Sept. 28, 2023

Language: Английский

Citations

22
Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression DOI Creative Commons
Nils Grotehans, Lynn McGarry, Hendrik Nolte

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(18)

Published: July 13, 2023

Replication of the mitochondrial genome and expression genes it encodes both depend on a sufficient supply nucleotides to mitochondria. Accordingly, dysregulated nucleotide metabolism not only destabilises genome, but also affects its transcription. Here, we report that nucleoside diphosphate kinase, NME6, supplies mitochondria with pyrimidine ribonucleotides are necessary for transcription genes. Loss NME6 function leads depletion transcripts, as well destabilisation electron transport chain impaired oxidative phosphorylation. These deficiencies rescued by an exogenous ribonucleosides. Moreover, is required maintenance DNA when access cytosolic deoxyribonucleotides limited. Our results therefore reveal important role ribonucleotide salvage in gene expression.

Language: Английский

Citations

16
Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA DOI Creative Commons

Emi Matsumoto,

Taeko Sasaki, Tetsuya Higashiyama

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 21, 2025

Mitochondrial DNA (mtDNA) is organized with proteins into mitochondrial nucleoid (mt-nucleoid). The mt-nucleoid a unit for the maintenance and function of mtDNA. regulator chromosome condensation 1-like protein (RCC1L) performs various functions in mitochondria, including translation, but its involvement regulating unknown. Herein, we found that human RCC1L was required to maintain mt-nucleoids Human has three splicing isoforms: RCC1LV1, RCC1LV2, RCC1LV3. Knockout (KO) cells lacking all isoforms, which were lethal without pyruvate uridine, exhibited decrease mtDNA, along swollen fragmented mitochondria. Among only RCC1LV1 recovered phenotypes observed KO cells. As treatment wild-type chloramphenicol, translation inhibitor, did not lead accompanied by mtDNA depletion, solely attributed impaired translation. Using conditional cells, rapid during specific period following loss. Our findings indicate regulates besides role translational regulation.

Language: Английский

Citations

0
Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome DOI Creative Commons
Penghao Xu, Taehwan Yang, Deepali L. Kundnani

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(3), P. 1207 - 1225

Published: Dec. 20, 2023

Abundant ribonucleoside-triphosphate (rNTP) incorporation into DNA by polymerases in the form of ribonucleoside monophosphates (rNMPs) is a widespread phenomenon nature, resulting DNA-structural change and genome instability. The rNMP distribution, characteristics, hotspots association with metabolic processes human mitochondrial (hmtDNA) remain mostly unknown. Here, we utilize ribose-seq technique to capture embedded rNMPs hmtDNA six different cell types. In most types, are preferentially on light strand strong bias towards rCMPs; while liver-tissue cells, predominately found heavy strand. We uncover common conserved rNMP-enriched zones across entire hmtDNA, including control region, which links presence frequent replication-failure events. show correlation between coding-sequence size rNMP-embedment frequency per nucleotide non-template, all supporting transient RNA-DNA hybrids preceding light-strand replication. Moreover, detect patterns that only partly types distinct from those yeast mtDNA. study opens new research directions understand biology genomic rNMPs.

Language: Английский

Citations

4
Insight into the role of mitochondrion-related gene anchor signature in mitochondrial dysfunction of neutrophilic asthma DOI Creative Commons

Lu Lin,

Zeng-hua Liao,

Chaoqian Li

et al.

Journal of Asthma, Journal Year: 2024, Volume and Issue: 61(9), P. 912 - 929

Published: Jan. 31, 2024

At present, targeting molecular-pharmacological therapy is still difficult in neutrophilic asthma. The investigation aims to identify and validate mitochondrion-related gene signatures for diagnosis specific therapeutics

Language: Английский

Citations

1
Mitochondrial NME6: A Paradigm Change within the NME/NDP Kinase Protein Family? DOI Creative Commons
Bastien Lucien Jean Proust, Maja Herak Bosnar, Helena Ćetković

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1278 - 1278

Published: July 30, 2024

Eukaryotic NMEs/NDP kinases are a family of 10 multifunctional proteins that occur in different cellular compartments and interact with various components (proteins, membranes, DNA). In contrast to the well-studied Group I NMEs (NME1–4), little is known about more divergent II (NME5–9). Three recent publications now shed new light on NME6. First, NME6 third mitochondrial NME, largely localized matrix space, associated inner membrane. Second, while its monomeric form inactive, gains NDP kinase activity through interaction RCC1L. This challenges current notion mammalian require formation hexamers become active. The complexes between RCC1L, likely heterodimers, seemingly obviates necessity for hexamer formation, stabilizing kinase-competent conformation. Third, involved gene maintenance expression by providing (d)NTPs replication transcription (in particular pyrimidine nucleotides) less characterized mechanism supports mitoribosome function. review offers an overview NME evolution structure highlights insight into findings position as most comprehensively studied protein may even suggest it paradigm related members.

Language: Английский

Citations

1
Mitochondrial Labeling with Mulberrin-Cy3: A New Fluorescent Probe for Live Cell Visualization DOI Creative Commons
Gangxiang Yuan,

Yiwei Luo,

Qian Peng

et al.

Biosensors, Journal Year: 2024, Volume and Issue: 14(9), P. 428 - 428

Published: Sept. 5, 2024

Mitochondria, crucial intracellular organelles, are central to energy metabolism, signal transduction, apoptosis, calcium homeostasis, and a myriad of other biological processes, making them focal point in diverse research fields. The capacity fluorescently label visually track mitochondria is for understanding their roles. We present mulberrin-Cy3, novel small molecule fluorescent probe that selectively labels animal cells, including cancer with relative ease. This protocol details the synthesis mulberrin-Cy3 its use visualizing living cells. straightforward time-efficient, labeling method more accessible than traditional approaches, providing cost-effective option mitochondrial visualization at room temperature. rapid, effective achieved within 5 min incubation. stable brighter, offering significant advantage over existing methods. Mulberrin-Cy3 represents promising compound, researchers experimental tool explore complex functions mitochondria. innovation has potential significantly advance our comprehension dynamics role cellular health disease.

Language: Английский

Citations

1
Effectively utilizing publicly available databases for cancer target evaluation DOI Creative Commons

Daniel R. Croft,

Puja Lodhia,

Sofia Lourenço

et al.

NAR Cancer, Journal Year: 2023, Volume and Issue: 5(3)

Published: June 9, 2023

Abstract The majority of compounds designed against cancer drug targets do not progress to become approved drugs, mainly due lack efficacy and/or unmanageable toxicity. Robust target evaluation is therefore required before progressing through the discovery process reduce high attrition rate. There are a wealth publicly available databases that can be mined generate data as part evaluation. It can, however, challenging learn what available, how and when they should used, understand associated limitations. Here, we have compiled present key, freely accessible easy-to-use house informative datasets from in vitro, vivo clinical studies. We also highlight comprehensive review aim bring together information multiple sources into one-stop portals. In post-genomics era, key objective exploit extensive cell, animal patient characterization order deliver precision medicine on patient-specific basis. Effective utilization highlighted will go some way towards supporting research community achieve these aims.

Language: Английский

Citations

3