{"doi":"10.1038/s41598-021-98722-1","title":"DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart","abstract":"DJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress-the non-enzymatic glycosylation of proteins. However, specific proteins protected from glycative stress by DJ-1 are not known. Given that mitochondrial electron transport proteins have a propensity for being targets of glycative stress, we investigated if DJ-1 regulates the glycation of Complex I and Complex III after myocardial ischemia-reperfusion (I/R) injury. Initial studies found that DJ-1 localized to the mitochondria and increased its interaction with Complex I and Complex III 3 days after the onset of myocardial I/R injury. Next, we investigated the role DJ-1 plays in modulating glycative stress in the mitochondria. Analysis revealed that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of glycative stress following I/R. Additionally, Complex I and Complex III glycation were found to be at higher levels in DJ-1 KO hearts. This corresponded with reduced complex activities, as well as reduced mitochondrial oxygen consumption ant ATP synthesis in the presence of pyruvate and malate. To further determine if DJ-1 influenced the glycation of the complexes, an adenoviral approach was used to over-express the active form of DJ-1(AAV9-DJ1ΔC). Under I/R conditions, the glycation of Complex I and Complex III were attenuated in hearts treated with AAV9-DJ1ΔC. This was accompanied by improvements in complex activities, oxygen consumption, and ATP production. Together, this data suggests that cardiac DJ-1 maintains Complex I and Complex III efficiency and mitochondrial function during the recovery from I/R injury. In elucidating a specific mechanism for DJ-1's role in the post-ischemic heart, these data break new ground for potential therapeutic strategies using DJ-1 as a target.","journal":"Scientific Reports","year":2021,"id":188006,"datarank":0.7164888723806586,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.27482302550569254,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.27482302550569254,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":14,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":748295,"name":"Rohini Polavarapu","orcid":"0000-0002-2320-6103","position":1,"is_corresponding":false},{"id":272044,"name":"Lih‐Shen Chin","orcid":"0000-0002-0817-0368","position":2,"is_corresponding":false},{"id":348382,"name":"Lian Li","orcid":"0000-0003-0097-1184","position":3,"is_corresponding":false},{"id":748296,"name":"Yuuki Shimizu","orcid":"0000-0003-3103-1160","position":4,"is_corresponding":false},{"id":407559,"name":"John W. Calvert","orcid":"0000-0001-6858-6042","position":5,"is_corresponding":false},{"id":748983,"name":"Yvanna Pantner","orcid":null,"position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:49:05.976005Z","pmid":"34593886","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":[]}