{"doi":"10.1073/pnas.1403521111","title":"Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>There are hundreds to thousands of copies of mitochondrial DNA (mtDNA) in each human cell in contrast to only two copies of nuclear DNA. High-frequency pathogenic mtDNA mutations have been found in patients with classic mitochondrial diseases, premature aging, cancers, and neurodegenerative diseases. In this study we investigated the distribution of heteroplasmic mutations, their pathogenic potential, and their underlying evolutionary forces using genome sequence data from the 1000 Genomes Project. Our results demonstrated the prevalence of low-frequency high-pathogenic-potential mtDNA mutations in healthy human individuals. These deleterious mtDNA mutations, when reaching high frequency, could provide a likely source of mitochondrial dysfunction. Managing the expansion of deleterious mtDNA mutations could be a promising means of preventing disease progression.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2014,"id":598220,"datarank":0.8652481493690659,"base_score":5.768320995793772,"endowment":5.768320995793772,"self_citation_contribution":0.8652481493690659,"citation_network_contribution":0.0,"self_endowment_contribution":0.8652481493690659,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":319,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320462,"name":"Jian Lu","orcid":"0000-0002-0267-9243","position":1,"is_corresponding":false},{"id":1360409,"name":"Fei Ma","orcid":"0009-0009-7422-6786","position":2,"is_corresponding":false},{"id":54976,"name":"Alon Keinan","orcid":"0000-0002-9760-1122","position":3,"is_corresponding":false},{"id":424592,"name":"Zhenglong Gu","orcid":"0000-0002-7733-432X","position":4,"is_corresponding":false},{"id":361139,"name":"Kaixiong Ye","orcid":"0000-0003-4658-7292","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>There are hundreds to thousands of copies of mitochondrial DNA (mtDNA) in each human cell in contrast to only two copies of nuclear DNA. High-frequency pathogenic mtDNA mutations have been found in patients with classic mitochondrial diseases, premature aging, cancers, and neurodegenerative diseases. In this study we investigated the distribution of heteroplasmic mutations, their pathogenic potential, and their underlying evolutionary forces using genome sequence data from the 1000 Genomes Project. Our results demonstrated the prevalence of low-frequency high-pathogenic-potential mtDNA mutations in healthy human individuals. These deleterious mtDNA mutations, when reaching high frequency, could provide a likely source of mitochondrial dysfunction. Managing the expansion of deleterious mtDNA mutations could be a promising means of preventing disease progression.</jats:p>","is_dataset_classified":null,"base_score":5.768320995793772,"endowment":5.768320995793772,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25002485","pmcid":"PMC4115537","openalex_id":"https://openalex.org/W2020439255","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI085286","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"R01 HG006849","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"1R01AI085286","title":null}],"total_grants":3,"fwci":9.878,"citation_percentile":0.98870134,"influential_citations":0,"citation_trend":[{"year":2014,"count":11},{"year":2015,"count":18},{"year":2016,"count":29},{"year":2017,"count":18},{"year":2018,"count":25},{"year":2019,"count":25},{"year":2020,"count":27},{"year":2021,"count":30},{"year":2022,"count":23},{"year":2023,"count":12},{"year":2024,"count":85},{"year":2025,"count":10},{"year":2026,"count":6}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/content/pnas/111/29/10654.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/111/29/10654.full.pdf","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1403521111","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1403521111","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25002485","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4115537","host_type":"repository"}],"fields_of_study":["Mitochondrial Function and Pathology","Metabolism and Genetic Disorders","Metabolomics and Mass Spectrometry Studies","DNA, Mitochondrial","Health","Humans","Mitochondria","Mitochondrial Diseases","Polymorphism, Genetic","RNA, Transfer","Selection, Genetic"],"mesh_terms":["DNA, Mitochondrial","Health","Humans","Mitochondria","Polymorphism, Genetic","RNA, Transfer","Selection, Genetic","Mitochondrial Diseases"],"keywords":["Heteroplasmy","Mitochondrial DNA","Human mitochondrial genetics","Biology","Genetics","Genome","Mutation","Mitochondrial disease","Nuclear DNA","Mitochondrion","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T15:17:44.660369Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}