Reference : Mutations in RHOT1 disrupt ER-mitochondria contact sites interfering with calcium hom...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/39949
Mutations in RHOT1 disrupt ER-mitochondria contact sites interfering with calcium homeostasis and mitochondrial dynamics in Parkinson's disease.
English
Grossmann, Dajana mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Berenguer, Clara mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Bellet, Marie Estelle []
Scheibner, David [> >]
Bohler, Jill []
Massart, François mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Rapaport, Doron [> >]
Skupin, Alexander mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Fouquier d'Hérouël, Aymeric mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Sharma, Manu [> >]
Ghelfi, Jenny mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Rakovic, Aleksandar [> >]
Lichtner, Peter [> >]
Antony, Paul mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Dimmer, Kai Stefan [> >]
Fitzgerald, Julia Catherine [> >]
Grünewald, Anne mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
15-Jul-2019
Antioxidants & redox signaling
Yes
International
1523-0864
1557-7716
United States
[en] RHOT1 ; Miro1 ; Parkinson's disease ; mitochondria ; mitochondrial shape transition ; ER-mitochondrial contact
[en] OBJECTIVE: The outer mitochondrial membrane protein Miro1 is a crucial player in mitochondrial dynamics and calcium homeostasis. Recent evidence indicated that Miro1 mediates calcium-induced mitochondrial shape transition (MiST), which is a prerequisite for the initiation of mitophagy. Moreover, altered Miro1 protein levels have emerged as a shared feature of monogenic and sporadic Parkinson's disease (PD), but, so far, no disease-associated variants in RHOT1 have been identified. RESULTS: Here, for the first time, we describe heterozygous RHOT1 mutations in two PD patients (het c.815G>A; het c.1348C>T) and identified mitochondrial phenotypes with reduced mitochondrial mass in patient-derived cellular models. Both mutations lead to decreased ER-mitochondrial contact sites and calcium dyshomeostasis. As a consequence, energy metabolism was impaired, which in turn lead to increased mitophagy. CONCLUSION: In summary, our data support the role of Miro1 in maintaining calcium homeostasis and mitochondrial quality control in PD.
Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Integrative Cell Signalling (Skupin Group)
FNR: PEARL (P13/6682797/Krüger), MiRisk-PD (MiRisk‐PD, C17/BM/11676395), CASCAD (7975668), INTER/BMBF/13/04, NCER-PD, FNR9631103. ; DFG: KR2119/8‐1, DI 1386/2‐1, FOR2488 ; NIH: P41 GM103426 ; BMBF: Mito‐PD 031 A 430 A ; JPND Courage-PD
Researchers ; Professionals ; Students ; General public
http://hdl.handle.net/10993/39949
10.1089/ars.2018.7718
https://www.liebertpub.com/doi/pdfplus/10.1089/ars.2018.7718
H2020 ; 692320 - CENTRE-PD - TWINNING for a Comprehensive Clinical Centre for the Diagnosis and Treatment of Parkinson's Disease
FnR ; FNR11676395 > Rejko Krüger > MiRisk-PD > Mitochondrial Risk factors in Parkinson's Disease > 01/03/2018 > 28/02/2021 > 2017

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Limited access
Grossmann2019.AntioxRedoxSign.pdfAuthor postprint2.83 MBRequest a copy

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.