{"doi":"10.1152/ajpcell.00649.2005","title":"Bidirectional Ca<sup>2+</sup> coupling of mitochondria with the endoplasmic reticulum and regulation of multimodal Ca<sup>2+</sup> entries in rat brown adipocytes","abstract":"<jats:p> How the endoplasmic reticulum (ER) and mitochondria communicate with each other and how they regulate plasmalemmal Ca<jats:sup>2+</jats:sup> entry were studied in cultured rat brown adipocytes. Cytoplasmic Ca<jats:sup>2+</jats:sup> or Mg<jats:sup>2+</jats:sup> and mitochondrial membrane potential were measured by fluorometry. The sustained component of rises in cytoplasmic Ca<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) produced by thapsigargin was abolished by removing extracellular Ca<jats:sup>2+</jats:sup>, depressed by depleting extracellular Na<jats:sup>+</jats:sup>, and enhanced by raising extracellular pH. FCCP, dinitrophenol, and rotenone caused bi- or triphasic rises in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>, in which the first phase was accompanied by mitochondrial depolarization. The FCCP-induced first phase was partially inhibited by oligomycin but not by ruthenium red, cyclosporine A, U-73122, a Ca<jats:sup>2+</jats:sup>-free EGTA solution, and an Na<jats:sup>+</jats:sup>-free solution. The FCCP-induced second phase paralleling mitochondrial repolarization was partially blocked by removing extracellular Ca<jats:sup>2+</jats:sup> and fully blocked by oligomycin but not by thapsigargin or an Na<jats:sup>+</jats:sup>-deficient solution, was accompanied by a rise in cytoplasmic Mg<jats:sup>2+</jats:sup> concentration, and was summated with a high pH-induced rise in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>, whereas the extracellular Ca<jats:sup>2+</jats:sup>-independent component was blocked by U-73122 and cyclopiazonic acid. The FCCP-induced third phase was blocked by removing Ca<jats:sup>2+</jats:sup> but not by thapsigargin, depressed by decreasing Na<jats:sup>+</jats:sup>, and enhanced by raising pH. Cyclopiazonic acid-evoked rises in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> in a Ca<jats:sup>2+</jats:sup>-free solution were depressed after FCCP actions. Thus mitochondrial uncoupling causes Ca<jats:sup>2+</jats:sup> release, activating Ca<jats:sup>2+</jats:sup> release from the ER and store-operated Ca<jats:sup>2+</jats:sup> entry, and directly elicits a novel plasmalemmal Ca<jats:sup>2+</jats:sup> entry, whereas Ca<jats:sup>2+</jats:sup> release from the ER activates Ca<jats:sup>2+</jats:sup> accumulation in, or release from, mitochondria, indicating bidirectional mitochondria-ER couplings in rat brown adipocytes. </jats:p>","journal":"American Journal of Physiology-Cell Physiology","year":2007,"id":24961,"datarank":0.9681645885466501,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.5346088248622254,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.5346088248622254,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":14,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":148191,"name":"Yoko Higure","orcid":null,"position":1,"is_corresponding":false},{"id":148192,"name":"Hisashi Susaki","orcid":null,"position":2,"is_corresponding":false},{"id":148193,"name":"Ryotaro Hayato","orcid":null,"position":3,"is_corresponding":false},{"id":148194,"name":"Kenji Kuba","orcid":null,"position":4,"is_corresponding":false},{"id":148190,"name":"Masako Kuba","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16987997","pmcid":null,"openalex_id":"https://openalex.org/W2113286694","authors":[],"funders":[],"total_grants":0,"fwci":0.5452,"citation_percentile":0.65560109,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2014,"count":1},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2022,"count":3},{"year":2024,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://journals.physiology.org/doi/pdf/10.1152/ajpcell.00649.2005","host_type":"publisher"},{"url":"https://doi.org/10.1152/ajpcell.00649.2005","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16987997","host_type":"repository"}],"fields_of_study":["Mitochondrial Function and Pathology","Adipose Tissue and Metabolism","Endoplasmic Reticulum Stress and Disease","Biology","Medicine","Adipocytes, Brown","Animals","Calcium","Calcium Signaling","Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone","Cells, Cultured","Cyclosporine","Endoplasmic Reticulum","Enzyme Inhibitors","Estrenes","Hydrogen-Ion Concentration","Indoles","Intracellular Fluid","Magnesium","Membrane Potential, Mitochondrial","Mitochondria","Oligomycins","Pyrrolidinones","Rats","Rotenone","Sodium","Thapsigargin","Uncoupling Agents"],"mesh_terms":["Animals","Calcium","Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone","Cells, Cultured","Endoplasmic Reticulum","Enzyme Inhibitors","Estrenes","Hydrogen-Ion Concentration","Indoles","Intracellular Fluid","Magnesium","Mitochondria","Oligomycins","Pyrrolidinones","Rotenone","Sodium","Uncoupling Agents","Cyclosporine","Thapsigargin","Calcium Signaling","Rats","Adipocytes, Brown","Membrane Potential, Mitochondrial"],"keywords":["Cyclopiazonic acid","Thapsigargin","Oligomycin","Ruthenium red","Extracellular","Endoplasmic reticulum","EGTA","Biophysics","Ryanodine receptor","Mitochondrion","Biology","Chemistry","Biochemistry","Calcium","ATPase"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:38:16.353605Z","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":[]}