{"doi":"10.1101/2020.08.31.275644","title":"A deeply conserved miR-1 dependent regulon supports muscle cell physiology","abstract":"Muscles are not only essential for force generation but are also key regulators of systemic energy homeostasis 1 . Both these roles rely heavily on mitochondria and lysosome function as providers of energy and building blocks, but also as metabolic sensors 2-4 . Perturbations in these organelles or their crosstalk lead to a wide range of pathologies 5 . Here, we uncover a deeply conserved regulon of mitochondria and lysosome homeostasis under control of the muscle-specific microRNA miR-1. Animals lacking miR-1 display a diverse range of muscle cell defects that have been attributed to numerous different targets 6 . Guided by the striking conservation of miR-1 and some of its predicted targets, we identified a set of direct targets that can explain the pleiotropic function of miR-1. miR-1-mediated repression of multiple subunits of the vacuolar ATPase (V-ATPase) complex, a key player in the acidification of internal compartments and a hub for metabolic signaling 7,8 , and of DCT-1/BNIP3, a mitochondrial protein involved in mitophagy and apoptosis 9,10 , accounts for the function of this miRNA in C. elegans . Surprisingly, although multiple V-ATPase subunits are upregulated in the absence of miR-1, this causes a loss-of-function of V-ATPase due to altered levels or stoichiometry, which negatively impact complex assembly. Finally, we demonstrate the conservation of the functional relationship between miR-1 and the V-ATPase complex in Drosophila .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122269,"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":0.9475,"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":563189,"name":"Emilio M. Santillán","orcid":"0000-0002-9113-5407","position":1,"is_corresponding":false},{"id":563190,"name":"Thomas Lendl","orcid":"0000-0003-4596-9512","position":2,"is_corresponding":false},{"id":563191,"name":"Anna Schrempf","orcid":"0000-0002-2146-2568","position":3,"is_corresponding":false},{"id":563192,"name":"Thomas L. Steinacker","orcid":"0000-0002-7244-5610","position":4,"is_corresponding":false},{"id":456998,"name":"Mila Asparuhova","orcid":"0000-0002-8597-4116","position":5,"is_corresponding":false},{"id":563193,"name":"Marlene Brandstetter","orcid":"0000-0002-8134-4985","position":6,"is_corresponding":false},{"id":241660,"name":"David Haselbach","orcid":"0000-0002-5276-5633","position":7,"is_corresponding":false},{"id":457000,"name":"Luisa Cochella","orcid":"0000-0003-4018-7722","position":8,"is_corresponding":false},{"id":456999,"name":"Paula Gutiérrez‐Pérez","orcid":"0000-0002-9364-9436","position":0,"is_corresponding":true}],"reference_count":67,"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":[]}