% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Baden:257563,
author = {Baden, Pascale and Perez, Maria Jose and Raji, Hariam and
Bertoli, Federico and Kalb, Stefanie and Illescas, María
and Spanos, Fokion and Giuliano, Claudio and Calogero,
Alessandra Maria and Oldrati, Marvin and Hebestreit, Hannah
and Cappelletti, Graziella and Brockmann, Kathrin and
Gasser, Thomas and Schapira, Anthony H V and Ugalde,
Cristina and Deleidi, Michela},
title = {{G}lucocerebrosidase is imported into mitochondria and
preserves complex {I} integrity and energy metabolism.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2023-00443},
pages = {1930},
year = {2023},
abstract = {Mutations in GBA1, the gene encoding the lysosomal enzyme
β-glucocerebrosidase (GCase), which cause Gaucher's
disease, are the most frequent genetic risk factor for
Parkinson's disease (PD). Here, we employ global proteomic
and single-cell genomic approaches in stable cell lines as
well as induced pluripotent stem cell (iPSC)-derived neurons
and midbrain organoids to dissect the mechanisms underlying
GCase-related neurodegeneration. We demonstrate that GCase
can be imported from the cytosol into the mitochondria via
recognition of internal mitochondrial targeting
sequence-like signals. In mitochondria, GCase promotes the
maintenance of mitochondrial complex I (CI) integrity and
function. Furthermore, GCase interacts with the
mitochondrial quality control proteins HSP60 and LONP1.
Disease-associated mutations impair CI stability and
function and enhance the interaction with the mitochondrial
quality control machinery. These findings reveal a
mitochondrial role of GCase and suggest that defective CI
activity and energy metabolism may drive the pathogenesis of
GCase-linked neurodegeneration.},
keywords = {Humans / Glucosylceramidase: genetics / Glucosylceramidase:
metabolism / Proteomics / Parkinson Disease: metabolism /
Mitochondria: genetics / Mitochondria: metabolism / Energy
Metabolism: genetics / Mutation / Lysosomes: metabolism /
alpha-Synuclein: metabolism / Mitochondrial Proteins:
metabolism / ATP-Dependent Proteases: metabolism /
Glucosylceramidase (NLM Chemicals) / alpha-Synuclein (NLM
Chemicals) / LONP1 protein, human (NLM Chemicals) /
Mitochondrial Proteins (NLM Chemicals) / ATP-Dependent
Proteases (NLM Chemicals)},
cin = {AG Deleidi / AG Gasser 1},
ddc = {500},
cid = {I:(DE-2719)1210011 / I:(DE-2719)1210000},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37024507},
pmc = {pmc:PMC10079970},
doi = {10.1038/s41467-023-37454-4},
url = {https://pub.dzne.de/record/257563},
}