ArticleMolecular omics2022
Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS.
Article in Molecular omics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Mitochondrial mutation status, symptom prevalence, and neuroimaging characteristics in MELAS: a systematic review and meta analysis.Orphanet journal of rare diseases · 2026Pooled it
- Mitochondria-centred metabolomic map of inclusion body myositis: sex-specific alterations in central carbon metabolism.Annals of the rheumatic diseases · 2025Article
- Mitochondria regulate MR1 protein expression and produce self-metabolites that activate MR1-restricted T cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HBimmCue: A Versatile Fluorescent Probe for Multi-Scale Imaging of Lipid Polarity and Membrane Order in Inner Mitochondrial Membrane.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Evaluating sample normalization methods for MS-based multi-omics and the application to a neurodegenerative mouse model.The Analyst · 2025Article
- Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons.Journal of proteome research · 2024Article
- Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure.Scientific reports · 2024Article
- Arginine Supplementation in MELAS Syndrome: What Do We Know about the Mechanisms?International journal of molecular sciences · 2024Review
- An evaluation of untargeted metabolomics methods to characterize inborn errors of metabolism.Molecular genetics and metabolism · 2024Review
- Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Article
- Protein Contaminants Matter: Building Universal Protein Contaminant Libraries for DDA and DIA Proteomics.Journal of proteome research · 2022Article
- Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics.Journal of visualized experiments : JoVE · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid β-oxidation. The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion. In conclusion, we demonstrated an integrated proteomic and metabolomic strategy for patient-derived fibroblasts, which has great clinical potential to discover therapeutic targets and design personalized interventions after validation with a larger patient cohort in the future.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.