{"doi":"10.1016/j.molmet.2022.101560","title":"Nicotinamide riboside alleviates exercise intolerance in ANT1-deficient mice","abstract":"Mitochondrial disorders are often characterized by muscle weakness and fatigue. Null mutations in the heart-muscle adenine nucleotide translocator isoform 1 (ANT1) of both humans and mice cause cardiomyopathy and myopathy associated with exercise intolerance and muscle weakness. Here we decipher the molecular underpinnings of ANT1-deficiency-mediated exercise intolerance. This was achieved by correlating exercise physiology, mitochondrial function and metabolomics of mice deficient in ANT1 and comparing this to control mice. We demonstrate a peripheral limitation of skeletal muscle mitochondrial respiration and a reduced complex I respiration in ANT1-deficient mice. Upon exercise, this results in a lack of NAD+ leading to a substrate limitation and stalling of the TCA cycle and mitochondrial respiration, further limiting skeletal muscle mitochondrial respiration. Treatment of ANT1-deficient mice with nicotinamide riboside increased NAD+ levels in skeletal muscle and liver, which increased the exercise capacity and the mitochondrial respiration. Increasing NAD+ levels with nicotinamide riboside can alleviate the exercise intolerance associated to ANT1-deficiency, indicating the therapeutic potential of NAD+-stimulating compounds in mitochondrial myopathies.","journal":"Molecular Metabolism","year":2022,"id":254613,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":899949,"name":"Jessica Huang","orcid":"0000-0002-9726-1746","position":1,"is_corresponding":false},{"id":893331,"name":"Arrienne Butic","orcid":null,"position":2,"is_corresponding":false},{"id":902343,"name":"Caroline E Perry","orcid":null,"position":3,"is_corresponding":false},{"id":668145,"name":"Tal Yardeni","orcid":"0000-0003-3119-0305","position":4,"is_corresponding":false},{"id":762537,"name":"Wendy Tan","orcid":null,"position":5,"is_corresponding":false},{"id":900380,"name":"Ryan Morrow","orcid":null,"position":6,"is_corresponding":false},{"id":231765,"name":"Joseph A. Baur","orcid":"0000-0001-8262-6549","position":7,"is_corresponding":false},{"id":227783,"name":"Douglas C. Wallace","orcid":"0000-0002-7480-8278","position":8,"is_corresponding":false},{"id":668776,"name":"Patrick M. Schaefer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:08.518416Z","pmid":"35940554","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":[]}