Mitochondrial-derived microproteins: from discovery to function DOI Creative Commons
Kelvin Yen, Brendan Miller, Hiroshi Kumagai

et al.

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Given the uniqueness of mitochondria, and fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery an increasing number from this organelle importance mitochondria to cellular organismal health make it a priority study novel class proteins in search possible therapeutic targets cures. In review, we discuss history MDP discovery, describe function each MDP, conclude with future goals techniques help discover more MDPs.

Language: Английский

Mitochondrial diseases: from molecular mechanisms to therapeutic advances DOI Creative Commons
Hu Wen,

Hui Deng,

Bingyan Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 9, 2025

Abstract Mitochondria are essential for cellular function and viability, serving as central hubs of metabolism signaling. They possess various metabolic quality control mechanisms crucial maintaining normal activities. Mitochondrial genetic disorders can arise from a wide range mutations in either mitochondrial or nuclear DNA, which encode proteins other contents. These defects lead to breakdown metabolism, such the collapse oxidative phosphorylation, one mitochondria’s most critical functions. diseases, common group disorders, characterized by significant phenotypic heterogeneity. Clinical symptoms manifest systems organs throughout body, with differing degrees forms severity. The complexity relationship between mitochondria diseases results an inadequate understanding genotype-phenotype correlation these historically making diagnosis treatment challenging often leading unsatisfactory clinical outcomes. However, recent advancements research technology have significantly improved our management conditions. translations mitochondria-related therapies actively progressing. This review focuses on physiological mitochondria, pathogenesis potential diagnostic therapeutic applications. Additionally, this discusses future perspectives diseases.

Language: Английский

Citations

4
Parkinson’s Disease: Biomarkers for Diagnosis and Disease Progression DOI Open Access
Rakesh Arya,

A. K. M. Ariful Haque,

Hemlata Shakya

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12379 - 12379

Published: Nov. 18, 2024

Parkinson's disease (PD) is a progressive neurological that causes both motor and nonmotor symptoms. While our understanding of putative mechanisms has advanced significantly, it remains challenging to verify biomarkers with sufficient evidence for regular clinical use. Clinical symptoms are the primary basis diagnosing disease, which can be mild in early stages overlap other disorders. As result, testing medical records mostly relied upon diagnosis, posing substantial challenges during initial diagnosis continuous monitoring. Recent biochemical, neuroimaging, genetic have helped us understand pathophysiology disease. This comprehensive study focuses on these biomarkers, were chosen based their relevance, methodological excellence, contribution field. Biochemical including α-synuclein glial fibrillary acidic protein (GFAP), predict severity progression. The dopaminergic system widely used as neuroimaging biomarker diagnose PD. Numerous genes genome wide association (GWAS) sites been related development research SNCA gene leucine-rich repeat kinase 2 (LRRK2) shown promising results. By evaluating current studies, this review intends uncover gaps validation use, while also highlighting improvements. It emphasizes need dependable reproducible indicators improving PD prognosis. These may open up new avenues progression tracking, personalized treatment programs.

Language: Английский

Citations

4
Multi-scale Neural Homeostasis Mechanisms: Insights into Neurodegenerative Diseases and Therapeutic Approaches, Including Exercise DOI Creative Commons
Ya Wang, Xuhui Chen, Cuntai Zhang

et al.

Advanced Exercise and Health Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Mechanism and Clinical Application Prospects of Mitochondrial DNA Single Nucleotide Polymorphism in Neurodegenerative Diseases DOI
Mengying Xu, Tianjiao Li, Xuan Liu

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 50(1)

Published: Dec. 14, 2024

Language: Английский

Citations

1
Investigating the Protective Role of the Mitochondrial 2158 T > C Variant in Parkinson's Disease DOI Creative Commons
Fulya Akçimen, Vesna van Midden, Sigvard Åkerman

et al.

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(9), P. 1645 - 1647

Published: June 28, 2024

A considerable portion of the risk for Parkinson's disease (PD) is attributed to genetic factors.1, 2 Several monogenic forms PD have been associated with mutations in genes encoding proteins involved mitochondrial function including PRKN and PINK1.1, 3, 4 Furthermore, human cell culture studies animal models offered evidence supporting presence disturbances PD.5 Hudson et al. proposed a protective role two DNA variants etiology.6 In an array-based genotyping study, authors showed that m.2158 T > C (p.Lys4Arg, rs41349444) variant SHLP2 reduced (P-value = × 10−2, OR 0.32). follow-up functional study by Kim demonstrated mutated protein was against dysfunction both vitro vivo PD.7 Nevertheless, association this has not confirmed large-scale sequencing datasets. To further investigate between PD, we conducted extensive characterization utilizing genome (GS) datasets, totaling 4358 cases 16,609 controls. Additionally, included 779 maternal proxies from All Us, considering transmission DNA. The homoplasmic allele frequency (AF) reported as 0.0066 gnomAD v.4.0.0.8 Considering limited capture rare arrays, challenge becomes more substantial GS offers comprehensive, accurate, high-resolution approach explore DNA, making it preferred method researchers studying complexity genetics diseases. Worldwide efforts, exemplified initiatives such Global Genetics Program (GP2; https://gp2.org/), enable us conduct unbiased screenings, facilitating associations significant statistical power. First, genotyped alignment files using mode.9 Details regarding sequencing, which includes sample variant-level quality control procedures, are presented supplementary materials. AF 0.012, 0.010, 0.013 AMP-PD, GP2, 100KGP, respectively. Subsequently, performed per-cohort logistic regression analyses adjusted age at onset controls, sex, first 10 principal components PLINK v.2.0 (https://www.cog-genomics.org/plink/2.0/).10 Our inverse-variance weighted meta-analysis11 did identify developing cohorts under (Table 1). utilized data various datasets while covariates sex age, support findings 2024, suggesting previous may represent type 1 error. investigation focused on evaluating accounting potential confounders. Utilizing genomes than 20,000 individuals provided power over 95% detect minimum relative 1.5 (https://csg.sph.umich.edu/abecasis/cats/gas_power_calculator/). results underscore significance leveraging multiple encompassing diverse populations validate before embarking studies. This work supported part Intramural Research National Institute Aging (NIA), Center Alzheimer's Related Dementias, within NIA Neurological Disorders Stroke. Data used preparation article were obtained (GP2). GP2 funded Aligning Science Across initiative implemented Michael J. Fox Foundation (https://gp2.org). computational resources Institutes Health high-performance computing Biowulf cluster (https://hpc.nih.gov). Accelerating Medicines Partnership® (AMP®) Disease (AMP® PD) Knowledge Platform. AMP® program public–private partnership managed Stroke (NINDS) (ASAP) initiative; Celgene Corporation, subsidiary Bristol-Myers Squibb Company; GlaxoSmithKline plc (GSK); Research; Pfizer Inc.; AbbVie Sanofi US Services Verily Life Sciences. For up-to-date information visit https://www.amp-pd.org. Us Health, Office Director: Regional Medical Centers: OT2 OD026549; OD026554; OD026557; OD026556; OD026550; OD 026552; OD026553; OD026548; OD026551; OD026555; IAA #: AOD 16037; Federally Qualified HHSN 263201600085 U; Center: 5 U2C OD023196; Biobank: U24 OD023121; Participant OD023176; Technology Systems OD023163; Communications Engagement: 3 OD023205; OD023206; Community Partners: OD025277; OD025315; OD025337; OD025276. addition, would be possible without its participants. research made through access generated 100,000 Genomes Project. Project Genomics England Limited (a wholly owned company Department Social Care). NHS England. Wellcome Trust, Cancer UK, Council also infrastructure. uses patients collected Service their care support. Care created 2013 introduce into healthcare conjunction affiliated are, or were, salaried seconded no financial interests disclose. F.A. V.v.M. wrote initial draft. S.C.A. contributed analysis. S.C.A., M.B.M., J.D.R. assisted acquisition Z.-H.F. analysis raw GP2. S.B.-C. conceptualized, designed, supervised project. edited reviewed final manuscript. hosted collaboration Partnership available via application website. case website (https://gp2.org; release 6 https://doi.org/10.5281/zenodo.10472143). Genotyping imputation, control, ancestry prediction, processing GenoTools (version 10), publicly GitHub. genomic restricted subject data. Access can following instructions workbench https://workbench.researchallofus.org/. Primary held secure Environment, registered users. Please see https://www.genomicsengland.co.uk/ information. algorithms tools openly https://github.com/GP2code/. code found online https://zenodo.org/records/11037328, https://github.com/GP2code/chrM.2158-analysis/. S1. Sequencing, sample, AMP-PD pipeline (https://github.com/GP2code/GenoTools). Sequencing Genome Centers Program. centers same protocols consisted polymerase chain reaction (PCR)-free 150 bp, paired-end libraries sequenced Illumina NovaSeq 6000 platform processed DRAGEN v3.4.12 software (https://developer.illumina.com/dragen). GRCh38 reference alignment. Phenotypic data, features, annotated Hail Researcher Workbench (https://support.researchallofus.org/hc/en-us/articles/6090679838100-How-to-Work-with-All-of-Us-Genomic-Data-Hail-Plink). We mode Analysis Toolkit version 4.5.0 (GATK Mutect2; https://software.broadinstitute.org/gatk/). each input call format (VCF) mtDNA previously applied v.3.1. As Mutect2 does provide joint calls, imputed non-mutant alleles references format. Therefore, unable depth coverage alleles. 100KGP described (https://re-docs.genomicsengland.co.uk/sample_qc/). screened multi-sample aggregated VCF. note: publisher responsible content functionality any supplied authors. Any queries (other missing content) should directed corresponding author article.

Language: Английский

Citations

0
Mitochondrial-derived microproteins: from discovery to function DOI Creative Commons
Kelvin Yen, Brendan Miller, Hiroshi Kumagai

et al.

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Given the uniqueness of mitochondria, and fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery an increasing number from this organelle importance mitochondria to cellular organismal health make it a priority study novel class proteins in search possible therapeutic targets cures. In review, we discuss history MDP discovery, describe function each MDP, conclude with future goals techniques help discover more MDPs.

Language: Английский

Citations

0