Tissue-specific apparent mtDNA heteroplasmy and its relationship with ageing and mtDNA gene expression DOI Creative Commons
Simon Wengert,

Xenofon Giannoulis,

Peter Kreitmaier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Heteroplasmy in the mitochondrial DNA (mtDNA) accumulates with age, but how much it occurs tissues and affects function physiology is not well-studied. Here we present a comprehensive tissue-specific map of mtDNA heteroplasmy mtRNA modifications, their relationships age gene expression. We propose robust variant calling pipeline for modifications using bulk RNAseq data from 49 GTEx, calibrated phenotype association framework both types variants. identify 109 associations between them donor 784 Of these, 7 18 show cell-type specificity within tissue. In addition, find 9 instances where these variations mediate effects on Finally, confirm previously identified mt-tRNA expression 5’, read- gene-level investigations reveal unmodeled complexities.

Language: Английский

Association of mitochondrial DNA copy number in peripheral blood with risk and prognosis in acute aortic syndrome DOI Creative Commons
Chun Yin, Ying Wang, Hao Yang

et al.

Journal of Molecular Diagnostics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review) DOI Creative Commons
Abdul Aziz Mohamed Yusoff, Siti Zulaikha Nashwa Mohd Khair, Siti Muslihah Abd Radzak

et al.

Molecular Medicine Reports, Journal Year: 2025, Volume and Issue: 31(3)

Published: Jan. 24, 2025

Renowned as a highly invasive and lethal tumor derived from neural stem cells in the central nervous system, glioblastoma (GBM) exhibits substantial histopathological variation genomic complexity, which drive its rapid progression therapeutic resistance. Alterations mitochondrial DNA (mtDNA) copy number (CN) serve crucial role GBM development progression, affecting various aspects of biology, including energy production, oxidative stress regulation cellular adaptability. Fluctuations mtDNA levels, whether elevated or diminished, can impair function, potentially disrupting phosphorylation amplifying reactive oxygen species generation, thereby fueling growth influencing treatment responses. Understanding mechanisms mtDNA‑CN variations, their interplay with genetic environmental elements microenvironment, is essential for advancing diagnostic strategies. Targeting alterations could strengthen efficacy, mitigate resistance ultimately enhance prognosis patients this aggressive brain tumor. The present review summarizes existing literature on alterations, specifically emphasizing variations association by surveying articles published between 1996 2024, sourced databases such Scopus, PubMed Google Scholar. In addition, provides brief overview genome architecture, knowledge regarding integrity CN, how mitochondria significantly impact tumorigenesis. This further presents information approaches restoring that contribute to optimized function improved health outcomes.

Language: Английский

Citations

0
Radiation-induced impacts on mitochondrial DNA and the transgenerational genomic instability DOI Creative Commons

Ryosuke Seino,

H Kubo,

Kai Nishikubo

et al.

Environment International, Journal Year: 2025, Volume and Issue: 196, P. 109315 - 109315

Published: Feb. 1, 2025

Language: Английский

Citations

0
Mitochondrial DNA Copy Number as a Hidden Player in the Progression of Multiple Sclerosis: A Bidirectional Two-Sample Mendelian Randomization Study DOI
Hani Sabaie,

Ali Taghavi Rad,

Mahnaz Sadeghi‐Shabestari

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Language: Английский

Citations

0
CRISPR‐Based Environmental Biosurveillance Assisted via Artificial Intelligence Design of Guide‐RNAs DOI Creative Commons
Benjamín Durán‐Vinet, Jo‐Ann L. Stanton, Gert‐Jan Jeunen

et al.

Environmental DNA, Journal Year: 2025, Volume and Issue: 7(3)

Published: May 1, 2025

ABSTRACT Environmental biosecurity challenges are intensifying as climate change and human activities accelerate the spread of invasive species, disrupting ecosystem composition, function, essential services. DNA (eDNA) has transformed traditional biosurveillance by detecting trace fragments left organisms in their surroundings, primarily applying quantitative polymerase chain reaction (qPCR) methods. However, qPCR presents challenges, including limited portability, reliance on precise thermal cycling, susceptibility to inhibitors. To address these enable field‐deployable monitoring, isothermal amplification techniques such recombinase (RPA) paired with clustered regularly interspaced short palindromic repeats associated proteins (CRISPR‐Cas) have been proposed promising alternatives. CRISPR‐Cas technology also searching optimizing a guide RNA (gRNA) that is highly sensitive no off‐target interactions for use an effective environmental tool. We present here development SENTINEL ( S mart E nvironmental N ucleic‐acid T racking using I nference from eural‐networks arly‐warning L ocalization) harnesses programmability, specificity sensitivity one‐pot RPA‐CRISPR‐Cas13a integrating accessible pre‐trained neural network assay design rapid deployment. challenged waterborne eDNA two marine sites invaded species not native New Zealand proof‐of‐concept fluorescence‐based tests: Sabella spallanzanii (Mediterranean fanworm) Undaria pinnatifida (Wakame). Off‐target effects were explored challenging assays gDNA suite co‐occurring species. presented robust, streamlined method incorporating trained network, achieving down 10 attomolar recombinant ~0.34 copies/μL samples 1 h, costing 3.5 USD per sample. There was 100% agreement between results qPCR‐based analysis samples. displayed activity when against 23 Thus, our study showcases SENTINEL's potential robust platform screening applications.

Language: Английский

Citations

0
Brain-body mitochondrial distribution patterns lack coherence and point to tissue-specific and individualized regulatory mechanisms DOI Creative Commons

Jack Devine,

Anna S. Monzel,

David Shire

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 22, 2024

Abstract Energy transformation capacity is generally assumed to be a coherent individual trait driven by genetic and environmental factors. This predicts that some individuals should have high others low mitochondrial oxidative phosphorylation (OxPhos) across organ systems. Here, we test this assumption using multi-tissue molecular enzymatic activities in mice humans. Across up 22 mouse tissues, neither OxPhos nor mtDNA density were correlated between tissues (median r = -0.01–0.16), indicating animals with one tissue can other tissues. Similarly, the correlation structure of RNAseq-based indices gene expression 45 from 948 women men (GTEx) showed small moderate coherence only (regions same brain), but not brain-body pairs person 0.01). Mitochondrial DNA copy number (mtDNAcn) also lacked organs Mechanistically, tissue-specific differences attributable part i) activation canonical energy sensing pathways including transcriptional coactivator PGC-111 integrated stress response (ISR), ii) proliferative activity Finally, identify subgroups (e.g., heart) skeletal muscle) who display different clinical phenotypic patterns. Taken together, these data raise possibility may contribute idiosyncratic distribution patterns associated inter-organ heterogeneity diversity among individuals.

Language: Английский

Citations

1
Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age DOI Creative Commons
Barbara Arbeithuber,

Kate Anthony,

Bonnie Higgins

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Summary Mitochondria, cellular powerhouses, harbor DNA (mtDNA) inherited from the mothers. MtDNA mutations can cause diseases, yet whether they increase with age in human germline cells—oocytes—remains understudied. Here, using highly accurate duplex sequencing of full-length mtDNA, we detected de novo single oocytes, blood, and saliva women between 20 42 years age. We found that, age, increased blood but not oocytes. In high allele frequencies (≥1%) were less prevalent coding than non-coding regions, whereas low (<1%) more uniformly distributed along suggesting frequency-dependent purifying selection. somatic tissues, caused elevated amino acid changes protein-coding positive or destructive Thus, mtDNA oocytes is protected against accumulation having functional consequences aging. These findings are particularly timely as humans tend to reproduce later life. Graphical abstract

Language: Английский

Citations

1
CRISPR-based environmental biosurveillance assisted via artificial intelligence design of guide-RNAs DOI Open Access
Benjamín Durán‐Vinet, Jo‐Ann L. Stanton, Gert‐Jan Jeunen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Environmental biosecurity challenges are worsening for aquatic ecosystems as climate change and increased anthropogenic pressures facilitate the spread of invasive species, thereby broadly impacting ecosystem composition, functioning, services. DNA (eDNA) has transformed traditional biomonitoring through detection trace fragments left by organisms in their surroundings, primarily application quantitative polymerase chain reaction (qPCR). However, qPCR presents challenges, including limited portability, reliance on precise thermal cycling, susceptibility to inhibitors. To address these enable field-deployable monitoring, isothermal amplification techniques such Recombinase Polymerase Amplification (RPA) paired with Clustered Regularly Interspaced Short Palindromic Repeats associated proteins (CRISPR-Cas) have been proposed alternatives. We report here development CORSAIR ( C RISPR-based envir O nmental biosu R veillance a S sisted via A rtificial I ntelligence guide- NAs), that harnesses programmability CRISPR-Cas technology, RPA artificial intelligence (AI)-based tool Activity-informed Design All-inclusive Patrolling Targets (ADAPT) deploy swift RPA-CRISPR-Cas13a-based method detects eDNA from two species proof concept: Sabella spallanzanii Undaria pinnatifida . showcased robust, streamlined augmented ADAPT, reaching high specificity when tested against co-occurring 100% agreement 12 PCR-benchmarked samples, sensitivity 0.34 copies uL -1 1 hour cost 3.5 USD per sample; thus highlighting powerful environmental biosurveillance platform nucleic acid detection. Graphical abstract

Language: Английский

Citations

0
Tissue-specific apparent mtDNA heteroplasmy and its relationship with ageing and mtDNA gene expression DOI Creative Commons
Simon Wengert,

Xenofon Giannoulis,

Peter Kreitmaier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Heteroplasmy in the mitochondrial DNA (mtDNA) accumulates with age, but how much it occurs tissues and affects function physiology is not well-studied. Here we present a comprehensive tissue-specific map of mtDNA heteroplasmy mtRNA modifications, their relationships age gene expression. We propose robust variant calling pipeline for modifications using bulk RNAseq data from 49 GTEx, calibrated phenotype association framework both types variants. identify 109 associations between them donor 784 Of these, 7 18 show cell-type specificity within tissue. In addition, find 9 instances where these variations mediate effects on Finally, confirm previously identified mt-tRNA expression 5’, read- gene-level investigations reveal unmodeled complexities.

Language: Английский

Citations

0