{"doi":"10.1093/jb/mvz069","title":"PINK1 import regulation at a crossroad of mitochondrial fate: the molecular mechanisms of PINK1 import","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase whose activity is tightly regulated by the mitochondrial health status. In response to mitochondrial damage, activated PINK1 can promote mitophagy, an autophagic elimination of damaged mitochondria, by cooperating with Parkin ubiquitin ligase. Loss-of-function of PINK1/Parkin-mediated mitophagy results in the accumulation of dysfunctional mitochondria, which could be one aetiology of Parkinson’s disease (PD). Within step-by-step signalling cascades of PINK1/Parkin-mediated mitophagy, mitochondrial damage-dependent PINK1 kinase activation is a critical step to trigger the mitophagy signal. Recent investigation of this process reveals that this stress-dependent PINK1 kinase activation is achieved by its regulated import into different mitochondrial compartments. Thus, PINK1 import regulation stands at an important crossroad to determine the mitochondrial fate—‘keep’ or ‘remove’? In this review, we will summarize how the PINK1 import is regulated in a mitochondrial health status-dependent manner and how this process could be pharmacologically modulated to activate the PINK1/Parkin pathway.</jats:p>","journal":"The Journal of Biochemistry","year":2019,"id":602302,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":299706,"name":"Shiori Sekine","orcid":"0000-0001-9962-833X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"PINK1 import regulation at a crossroad of mitochondrial fate: the molecular mechanisms of PINK1 import","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase whose activity is tightly regulated by the mitochondrial health status. In response to mitochondrial damage, activated PINK1 can promote mitophagy, an autophagic elimination of damaged mitochondria, by cooperating with Parkin ubiquitin ligase. Loss-of-function of PINK1/Parkin-mediated mitophagy results in the accumulation of dysfunctional mitochondria, which could be one aetiology of Parkinson’s disease (PD). Within step-by-step signalling cascades of PINK1/Parkin-mediated mitophagy, mitochondrial damage-dependent PINK1 kinase activation is a critical step to trigger the mitophagy signal. Recent investigation of this process reveals that this stress-dependent PINK1 kinase activation is achieved by its regulated import into different mitochondrial compartments. Thus, PINK1 import regulation stands at an important crossroad to determine the mitochondrial fate—‘keep’ or ‘remove’? In this review, we will summarize how the PINK1 import is regulated in a mitochondrial health status-dependent manner and how this process could be pharmacologically modulated to activate the PINK1/Parkin pathway.</jats:p>","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31504668","pmcid":null,"openalex_id":"https://openalex.org/W2972511279","authors":[],"funders":[{"funder_name":"Aging Institute of UPMC and the University of Pittsburgh","grant_id":"","title":null}],"total_grants":1,"fwci":2.2767,"citation_percentile":0.89330683,"influential_citations":0,"citation_trend":[{"year":2020,"count":6},{"year":2021,"count":13},{"year":2022,"count":11},{"year":2023,"count":11},{"year":2024,"count":4},{"year":2025,"count":8},{"year":2026,"count":3}],"oa_status":"closed","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"http://academic.oup.com/jb/advance-article-pdf/doi/10.1093/jb/mvz069/30073745/mvz069.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/jb/mvz069","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31504668","host_type":"repository"}],"fields_of_study":["Mitochondrial Function and Pathology","Autophagy in Disease and Therapy","Neutrophil, Myeloperoxidase and Oxidative Mechanisms"],"mesh_terms":["Protein Domains","PTEN-Induced Putative Kinase","Humans","Metalloendopeptidases","Mitochondria","Parkinson Disease","Protein Kinases","Signal Transduction","Protein Transport","Ubiquitin-Protein Ligases","Mitophagy"],"keywords":["PINK1","Cell biology","Mitochondrion","Chemistry","Business","Mitophagy","Biology","Biochemistry","Apoptosis","Autophagy","Parkinson’s Disease","Mitochondrial Import","Mitochondrial Protease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T18:58:48.689368Z","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":[]}