Journal Article

MSTO1 is a cytoplasmic pro‐mitochondrial fusion protein

Naghdi, Shamim, Várnai, Péter, Horváth, Attila, Hajnóczky, György, Balicza, Peter, Seifert, Erin L, Gal, Aniko, Molnar, Maria Judit, Gyuris, Tibor, Nagy, Laszlo, Weaver, David, Joseph, Suresh K

2017

Overview

The protein MSTO1 has been localized to mitochondria and linked to mitochondrial morphology, but its specific role has remained unclear. 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. 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. MSTO1 likely has a physiologically relevant role in mitochondrial morphogenesis by supporting mitochondrial fusion. § Synopsis MSTO1 has been localized to mitochondria and linked to their morphology but its role remained unclear. Here, an MSTO1 loss‐of‐function mutation is shown to be associated with a human disorder showing mitochondrial involvement. Mutation of MSTO1 is documented in a family of patients with multisystem disease. MSTO1‐deficient patient cells and HeLa cells show impaired mitochondrial morphology and fusion that can be rescued by MSTO1 overexpression. MSTO1 is a soluble cytoplasmic protein that likely interacts with the mitochondrial fusion proteins. Graphical Abstract MSTO1 has been localized to mitochondria and linked to their morphology but its role remained unclear. Here, an MSTO1 loss‐of‐function mutation is shown to be associated with a human disorder showing mitochondrial involvement.

• Publisher: Nature Publishing Group UK,EMBO Press,Springer Nature
• Subject: Ataxia / Bioenergetics / Cytoplasm / EMBO16 / EMBO21 / Fibroblasts / Fusion protein / Lactic acid / misato / Mitochondria / mitochondrial disease / Mitochondrial DNA / mitochondrial fusion / Morphogenesis / Morphology / mRNA / MSTO1 / Mutation / Myopathy / Neurodevelopmental disorders / Proteins / Research Article