| First Author | Huang E | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1399 |
| PubMed ID | 29123128 | Mgi Jnum | J:255916 |
| Mgi Id | MGI:6106224 | Doi | 10.1038/s41467-017-01435-1 |
| Citation | Huang E, et al. (2017) PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress. Nat Commun 8(1):1399 |
| abstractText | Mutations in PTEN-induced kinase 1 (PINK1) result in a recessive familial form of Parkinson''s disease (PD). PINK1 loss is associated with mitochondrial Ca(2+) mishandling, mitochondrial dysfunction, as well as increased neuronal vulnerability. Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro. Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria. Expression of LETM1-T192E but not LETM1-wild type (WT) rescues mitochondrial calcium mishandling in PINK1-deficient neurons. Expression of both LETM1-WT and LETM1-T192E protects neurons against MPP(+)-MPTP-induced neuronal death in PINK1 WT neurons, whereas only LETM1-T192E protects neurons under conditions of PINK1 loss. Our findings delineate a mechanism by which PINK1 regulates mitochondrial Ca(2+) level through LETM1 and suggest a model by which PINK1 loss leads to deficient phosphorylation of LETM1 and impaired mitochondrial Ca(2+) transport.. |
