Mitochondrial proteolytic stress induced by loss of mortalin function is rescued by Parkin and PINK1.

ABSTRACT: The mitochondrial chaperone mortalin was implicated in Parkinson's disease (PD) because of its reduced levels in the brains of PD patients and disease-associated rare genetic variants that failed to rescue impaired mitochondrial integrity in cellular knockdown models. To uncover the molecular mechanisms underlying mortalin-related neurodegeneration, we dissected the cellular surveillance mechanisms related to mitochondrial quality control, defined the effects of reduced mortalin function at the molecular and cellular levels and investigated the functional interaction of mortalin with Parkin and PINK1, two PD-related proteins involved in mitochondrial homeostasis. We found that reduced mortalin function leads to: (1) activation of the mitochondrial unfolded protein response (UPR(mt)), (2) i

SUBMITTER: Burbulla LF 

PROVIDER: S-EPMC4001296 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature