{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hussain M"],"funding":["National Institute of Immunology","Science and Engineering Research Board","Department of Biotechnology, Ministry of Science and Technology","Department of Science and Technology, Ministry of Science and Technology","Council of Scientific and Industrial Research, India"],"pagination":["e3001139"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7959396"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(3)"],"pubmed_abstract":["Mutations in mitochondrial replicative polymerase PolγA lead to progressive external ophthalmoplegia (PEO). While PolγA is the known central player in mitochondrial DNA (mtDNA) replication, it is unknown whether a regulatory process exists on the mitochondrial outer membrane which controlled its entry into the mitochondria. We now demonstrate that PolγA is ubiquitylated by mitochondrial E3 ligase, MITOL (or MARCH5, RNF153). Ubiquitylation in wild-type (WT) PolγA occurs at Lysine 1060 residue via K6 linkage. Ubiquitylation of PolγA negatively regulates its binding to Tom20 and thereby its mitochondrial entry. While screening different PEO patients for mitochondrial entry, we found that a subset of the PolγA mutants is hyperubiquitylated by MITOL and interact less with Tom20. These PolγA var"],"journal":["PLoS biology"],"pubmed_title":["MITOL-dependent ubiquitylation negatively regulates the entry of PolγA into mitochondria."],"pmcid":["PMC7959396"],"funding_grant_id":["BT/PR23545/BRB/10/1593/2017","Batch 35/July 2019/10","37(1699)/17/EMR-11","JCB/2018/000013","EMR/2017/000541","BT/MED/30/SP11263/2015","BT/PR27681/GET/119/269/2018","DST/INSPIRE/04/2017/000088"],"pubmed_authors":["Kaur E","Mohammed A","Saifi S","Khan A","Priya S","Agarwal H","Hussain M","Sengupta S"],"additional_accession":[]},"is_claimable":false,"name":"MITOL-dependent ubiquitylation negatively regulates the entry of PolγA into mitochondria.","description":"Mutations in mitochondrial replicative polymerase PolγA lead to progressive external ophthalmoplegia (PEO). While PolγA is the known central player in mitochondrial DNA (mtDNA) replication, it is unknown whether a regulatory process exists on the mitochondrial outer membrane which controlled its entry into the mitochondria. We now demonstrate that PolγA is ubiquitylated by mitochondrial E3 ligase, MITOL (or MARCH5, RNF153). Ubiquitylation in wild-type (WT) PolγA occurs at Lysine 1060 residue via K6 linkage. Ubiquitylation of PolγA negatively regulates its binding to Tom20 and thereby its mitochondrial entry. While screening different PEO patients for mitochondrial entry, we found that a subset of the PolγA mutants is hyperubiquitylated by MITOL and interact less with Tom20. These PolγA var","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-04T20:35:54.157Z","creation":"2025-04-04T20:35:54.157Z"},"accession":"S-EPMC7959396","cross_references":{"pubmed":["33657094"],"doi":["10.1371/journal.pbio.3001139"]}}