| First Author | Müller-Rischart AK | Year | 2013 |
| Journal | Mol Cell | Volume | 49 |
| Issue | 5 | Pages | 908-21 |
| PubMed ID | 23453807 | Mgi Jnum | J:198144 |
| Mgi Id | MGI:5495588 | Doi | 10.1016/j.molcel.2013.01.036 |
| Citation | Muller-Rischart AK, et al. (2013) The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell 49(5):908-21 |
| abstractText | Parkin, a RING-between-RING-type E3 ubiquitin ligase associated with Parkinson's disease, has a wide neuroprotective activity, preventing cell death in various stress paradigms. We identified a stress-protective pathway regulated by parkin that links NF-kappaB signaling and mitochondrial integrity via linear ubiquitination. Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-kappaB essential modulator (NEMO), which is essential for canonical NF-kappaB signaling. As a result, the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-kappaB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death. Parkin-induced stress protection is lost in the absence of either NEMO or OPA1, but not in cells defective for the mitophagy pathway. Notably, in parkin-deficient cells linear ubiquitination of NEMO, activation of NF-kappaB, and upregulation of OPA1 are significantly reduced in response to TNF-alpha stimulation, supporting the physiological relevance of parkin in regulating this antiapoptotic pathway. |
