A new target for an old DUB: UCH-L1 regulates mitofusin-2 levels, altering mitochondrial morphology, function and calcium uptake.

ABSTRACT: UCH-L1 is a deubiquitinating enzyme (DUB), highly abundant in neurons, with a sub-cellular localization dependent on its farnesylation state. Despite UCH-L1's association with familial Parkinson's Disease (PD), the effects on mitochondrial bioenergetics and quality control remain unexplored. Here we investigated the role of UCHL-1 in mitochondrial dynamics and bioenergetics. We demonstrate that knock-down (KD) of UCH-L1 in different cell lines reduces the levels of the mitochondrial fusion protein Mitofusin-2, but not Mitofusin-1, resulting in mitochondrial enlargement and disruption of the tubular network. This was associated with lower tethering between mitochondria and the endoplasmic reticulum, consequently altering mitochondrial calcium uptake. Respiratory function was also altered, a

SUBMITTER: Cerqueira FM 

PROVIDER: S-EPMC7509235 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature