Journal Article

MSTO 1 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 MSTO 1 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, MSTO 1 mRNA and protein abundance are decreased, mitochondria display fragmentation, aggregation, and decreased network continuity and fusion activity. Short‐term silencing of MSTO 1 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 MSTO 1 to be localized in the cytoplasmic area with limited colocalization with mitochondria. MSTO 1 interacts with the fusion machinery as a soluble factor at the cytoplasm‐mitochondrial outer membrane interface. After plasma membrane permeabilization, MSTO 1 is released from the cells. MSTO 1 likely has a physiologically relevant role in mitochondrial morphogenesis by supporting mitochondrial fusion. § image MSTO 1 has been localized to mitochondria and linked to their morphology but its role remained unclear. Here, an MSTO 1 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. MSTO 1‐deficient patient cells and HeLa cells show impaired mitochondrial morphology and fusion that can be rescued by MSTO 1 overexpression. MSTO 1 is a soluble cytoplasmic protein that likely interacts with the mitochondrial fusion proteins.