MSTO 1 is a cytoplasmic pro‐mitochondrial fusion protein

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. §