MSTO1 is a cytoplasmic pro-mitochondrial fusion protein, whose mutation induces myopathy and ataxia in humans
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Tartalom: http://real.mtak.hu/74745/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
MSTO1 is a cytoplasmic pro-mitochondrial fusion protein, whose mutation induces myopathy and ataxia in humans
Létrehozó:
Gál, Anikó
Balicza, PĂ©ter
Weaver, D.
Naghdi, S.
Joseph, S. K.
Várnai, Péter
Nagy, László
Molnár, Mária Judit
Dátum:
2017
Téma:
QH3011 Biochemistry / biokémia
QH3015 Molecular biology / molekuláris biológia
Tartalmi leírás:
The protein MSTO1 has been localized to mitochondria and linked to mitochondrial morphology, but its specific role has remained unclear. We identified a c.22G > A (p.Val8Met) mutation of MSTO1 in patients with minor physical abnormalities, myopathy, ataxia, and neurodevelopmental impairments. Lactate stress test and myopathological results suggest mitochondrial dysfunction. In patient fibroblasts, MSTO1 mRNA and protein abundance are decreased, mitochondria display fragmentation, aggregation, and decreased network continuity and fusion activity. These characteristics can be reversed by genetic rescue. Short-term silencing of MSTO1 in HeLa cells reproduced the impairment of mitochondrial morphology and dynamics observed in the fibroblasts without damaging bioenergetics. At variance with a previous report, we find MSTO1 to be localized in the cytoplasmic area with limited colocalization with mitochondria. MSTO1 interacts with the fusion machinery as a soluble factor at the cytoplasm-mitochondrial outer membrane interface. After plasma membrane permeabilization, MSTO1 is released from the cells. Thus, an MSTO1 loss-of-function mutation is associated with a human disorder showing mitochondrial involvement. MSTO1 likely has a physiologically relevant role in mitochondrial morphogenesis by supporting mitochondrial fusion.
Nyelv:
angol
Típus:
Article
PeerReviewed
info:eu-repo/semantics/article
Formátum:
text
Azonosító:
Gál, Anikó and Balicza, Péter and Weaver, D. and Naghdi, S. and Joseph, S. K. and Várnai, Péter and Nagy, László and Molnár, Mária Judit (2017) MSTO1 is a cytoplasmic pro-mitochondrial fusion protein, whose mutation induces myopathy and ataxia in humans. EMBO MOLECULAR MEDICINE, 9 (6). pp. 967-984. ISSN 1757-4676
Kapcsolat:
https://doi.org/10.15252/emmm.201607058
MTMT:3236662; doi:10.15252/emmm.201607058