{"doi":"10.1101/2020.06.07.138917","title":"Mitophagy protects beta cells from inflammatory damage in diabetes","abstract":"Abstract Inflammatory damage contributes to β-cell failure in type 1 and 2 diabetes (T1D and T2D). Mitochondria are damaged by inflammatory signaling in β-cells, resulting in impaired bioenergetics and initiation of pro-apoptotic machinery. Hence, the identification of protective responses to inflammation could lead to new therapeutic targets. Here we report that mitophagy serves as a protective response to inflammatory stress in both human and rodent β-cells. Utilizing in vivo mitophagy reporters, we observed that diabetogenic pro-inflammatory cytokines induced mitophagy in response to nitrosative/oxidative mitochondrial damage. Mitophagy-deficient β-cells were sensitized to inflammatory stress, leading to the accumulation of fragmented dysfunctional mitochondria, increased β-cell death, and hyperglycemia. Overexpression of CLEC16A , a T1D gene and mitophagy regulator whose expression in islets is protective against T1D, ameliorated cytokine-induced human β-cell apoptosis. Thus, mitophagy promotes β-cell survival and prevents diabetes by countering inflammatory injury. Targeting this pathway has the potential to prevent β-cell failure in diabetes and may be beneficial in other inflammatory conditions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122146,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562905,"name":"Gemma L. Pearson","orcid":"0000-0003-4253-1830","position":1,"is_corresponding":false},{"id":562906,"name":"Vishal S. Parekh","orcid":"0000-0001-6349-4077","position":2,"is_corresponding":false},{"id":562907,"name":"Benjamin Thompson","orcid":"0000-0003-2035-1337","position":3,"is_corresponding":false},{"id":562908,"name":"Lisa Christen","orcid":"0000-0003-3664-2892","position":4,"is_corresponding":false},{"id":562909,"name":"Morgan A. Gingerich","orcid":"0000-0002-8442-0947","position":5,"is_corresponding":false},{"id":294184,"name":"Jie Zhu","orcid":"0000-0001-7941-4166","position":6,"is_corresponding":false},{"id":563871,"name":"Tracy Stromer","orcid":null,"position":7,"is_corresponding":false},{"id":348733,"name":"Jianhua Ren","orcid":"0000-0003-1109-8843","position":8,"is_corresponding":false},{"id":562910,"name":"Emma C. Reck","orcid":"0009-0003-0784-1312","position":9,"is_corresponding":false},{"id":563872,"name":"Biaoxin Chai","orcid":null,"position":10,"is_corresponding":false},{"id":299560,"name":"John A. Corbett","orcid":"0000-0002-1134-4664","position":11,"is_corresponding":false},{"id":354421,"name":"Thomas Mandrup‐Poulsen","orcid":"0000-0002-3215-9273","position":12,"is_corresponding":false},{"id":348735,"name":"Leslie S. Satin","orcid":"0000-0003-1355-8647","position":13,"is_corresponding":false},{"id":428027,"name":"Scott A. Soleimanpour","orcid":"0000-0001-6777-4498","position":14,"is_corresponding":false},{"id":562904,"name":"Vaibhav Sidarala","orcid":"0000-0002-8010-3418","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","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":[]}