{"doi":"10.1016/j.celrep.2024.114783","title":"Geranylgeranylated SCFFBXO10 regulates selective outer mitochondrial membrane proteostasis and function","abstract":"Compartment-specific cellular membrane protein turnover is not well understood. We show that FBXO10, the interchangeable component of the cullin-RING-ligase 1 complex, undergoes lipid modification with geranylgeranyl isoprenoid at cysteine953, facilitating its dynamic trafficking to the outer mitochondrial membrane (OMM). FBXO10 polypeptide lacks a canonical mitochondrial targeting sequence (MTS); instead, its geranylgeranylation at C953 and interaction with two cytosolic factors, cytosolic factor-like δ subunit of type 6 phosphodiesterase (PDE6δ; a prenyl-group-binding protein) and heat shock protein 90 (HSP90; a chaperone), orchestrate specific OMM targeting of prenyl-FBXO10. The FBXO10(C953S) mutant redistributes away from the OMM, impairs mitochondrial ATP production and membrane potential, and increases fragmentation. Phosphoglycerate mutase-5 (PGAM5) was identified as a potential substrate of FBXO10 at the OMM using comparative quantitative proteomics of enriched mitochondria. FBXO10 loss or expression of prenylation-deficient FBXO10(C953S) inhibited PGAM5 degradation, disrupted mitochondrial homeostasis, and impaired myogenic differentiation of human induced pluripotent stem cells (iPSCs) and murine myoblasts. Our studies identify a mechanism for FBXO10-mediated regulation of selective mitochondrial proteostasis potentially amenable to therapeutic intervention.","journal":"Cell Reports","year":2024,"id":443303,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":867962,"name":"Zahra Vasi","orcid":null,"position":1,"is_corresponding":false},{"id":1081853,"name":"Liping Jiang","orcid":"0000-0003-4045-0770","position":2,"is_corresponding":false},{"id":1257904,"name":"Shruthi Selvaraj","orcid":null,"position":3,"is_corresponding":false},{"id":867965,"name":"Rachel Ferguson","orcid":null,"position":4,"is_corresponding":false},{"id":1119315,"name":"Sanaz Salarvand","orcid":null,"position":5,"is_corresponding":false},{"id":867117,"name":"Anish Gudur","orcid":"0009-0001-1893-486X","position":6,"is_corresponding":false},{"id":867963,"name":"Ritika Adhikari","orcid":null,"position":7,"is_corresponding":false},{"id":1257905,"name":"V. Leyva Castillo","orcid":null,"position":8,"is_corresponding":false},{"id":1047320,"name":"Hagar Ismail","orcid":"0000-0003-4802-3888","position":9,"is_corresponding":false},{"id":266320,"name":"Avantika Dhabaria","orcid":"0000-0002-0799-3223","position":10,"is_corresponding":false},{"id":231337,"name":"Beatrix Ueberheide","orcid":"0000-0003-2512-0204","position":11,"is_corresponding":false},{"id":867118,"name":"Shafi Kuchay","orcid":"0000-0002-2197-9241","position":12,"is_corresponding":false},{"id":447246,"name":"Sameer Ahmed Bhat","orcid":"0000-0003-1172-9297","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:01:24.471942Z","pmid":"39306844","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":[]}