{"doi":"10.3389/fcell.2022.866210","title":"mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila","abstract":"High-fat diet (HFD)-induced obesity has become the major risk factor for the development of cardiovascular diseases, but the underlying mechanisms remain poorly understood. Here, we use Drosophila as a model to study the role of mTORC2 in HFD-induced mitochondrial fission and cardiac dysfunction. We find that knockdown of mTORC2 subunit rictor blocks HFD-induced mitochondrial fragmentation and Drp1 recruitment. Knockdown of rictor further impairs cardiac contractile function under HFD treatment. Surprisingly, knockdown of Akt , the major effector of mTORC2, did not affect HFD-induced mitochondrial fission. Similar to mTORC2 inhibition, knockdown of Drp1 blocks HFD-induced mitochondrial fragmentation and induces contractile defects. Furthermore, overexpression of Drp1 restored HFD-induced mitochondrial fragmentation in rictor knockdown flies. Thus, we uncover a novel function of mTORC2 in protecting the heart from HFD treatment through Drp1-dependent mitochondrial fission.","journal":"Frontiers in Cell and Developmental Biology","year":2022,"id":266614,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"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":332405,"name":"Kai Chang","orcid":"0000-0003-1051-9394","position":1,"is_corresponding":false},{"id":927217,"name":"Guillermo Requejo","orcid":null,"position":2,"is_corresponding":false},{"id":569975,"name":"Hua Bai","orcid":"0000-0003-2221-7545","position":3,"is_corresponding":false},{"id":797138,"name":"Peiduo Liu","orcid":"0009-0006-6270-5470","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:26:58.102271Z","pmid":"35912118","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":[]}