Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 한평림 | - |
dc.contributor.author | 손형진 | - |
dc.contributor.author | 김현석 | - |
dc.date.accessioned | 2016-08-27T04:08:24Z | - |
dc.date.available | 2016-08-27T04:08:24Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.other | OAK-14827 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/217151 | - |
dc.description.abstract | The failure to trigger mitophagy is implicated in the pathogenesis of familial Parkinson disease that is caused by PINK1 or Parkin mutations. According to the prevailing PINK1-Parkin signaling model, mitophagy is promoted by the mitochondrial translocation of Parkin, an essential PINK1-dependent step that occurs via a previously unknown mechanism. Here we determined that critical concentrations of NO was sufficient to induce the mitochondrial translocation of Parkin even in PINK1 deficiency, with apparent increased interaction of full-length PINK1 accumulated during mitophagy, with neuronal nitric oxide synthase (nNOS). Specifically, optimum levels of NO enabled PINK1-null dopaminergic neuronal cells to regain the mitochondrial translocation of Parkin, which appeared to be significantly suppressed by nNOS-null mutation. Moreover, nNOS-null mutation resulted in the same mitochondrial electron transport chain (ETC) enzyme deficits as PINK1-null mutation. The involvement of mitochondrial nNOS activation in mitophagy was further confirmed by the greatly increased interactions of full-length PINK1 with nNOS, accompanied by mitochondrial accumulation of phospho-nNOS (Ser(1412)) during mitophagy. Of great interest is that the L347P PINK1 mutant failed to bind to nNOS. The loss of nNOS phosphorylation and Parkin accumulation on PINK1-deficient mitochondria could be reversed in a PINK1-dependent manner. Finally, non-toxic levels of NO treatment aided in the recovery of PINK1-null dopaminergic neuronal cells from mitochondrial ETC enzyme deficits. In summary, we demonstrated the full-length PINK1-dependent recruitment of nNOS, its activation in the induction of Parkin translocation, and the feasibility of NO-based pharmacotherapy for defective mitophagy and ETC enzyme deficits in Parkinson disease. | - |
dc.language | English | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | Mitophagy | - |
dc.subject | Nitric Oxide | - |
dc.subject | Parkin | - |
dc.subject | Parkinson Disease | - |
dc.subject | PTEN-induced Putative Kinase 1 (PINK1) | - |
dc.subject | nNOS | - |
dc.title | Nitric Oxide Induction of Parkin Translocation in PTEN-induced Putative Kinase 1 (PINK1) Deficiency FUNCTIONAL ROLE OF NEURONAL NITRIC OXIDE SYNTHASE DURING MITOPHAGY | - |
dc.type | Article | - |
dc.relation.issue | 16 | - |
dc.relation.volume | 290 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 10325 | - |
dc.relation.lastpage | 10335 | - |
dc.relation.journaltitle | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.identifier.doi | 10.1074/jbc.M114.624767 | - |
dc.identifier.wosid | WOS:000353241100035 | - |
dc.identifier.scopusid | 2-s2.0-84927732333 | - |
dc.author.google | Han, Ji-Young | - |
dc.author.google | Kang, Min-Ji | - |
dc.author.google | Kim, Kyung-Hee | - |
dc.author.google | Han, Pyung-Lim | - |
dc.author.google | Kim, Hyun-Seok | - |
dc.author.google | Ha, Ji-Young | - |
dc.author.google | Son, Jin H. | - |
dc.contributor.scopusid | 한평림(7201947605) | - |
dc.contributor.scopusid | 손형진(7203086503) | - |
dc.contributor.scopusid | 김현석(57191717681) | - |
dc.date.modifydate | 20230901081001 | - |