Functional prediction and physiological characterization of a novel short trans-membrane protein 1 (Stmp1) as a subunit of mitochondrial respiratory complexes

Mitochondrial respiration is mediated by a set of multi-subunit assemblies of proteins that are embedded in the mitochondrial inner membranes. Respiratory complexes do not only contain central catalytic subunits essential for the bio-energetic transformation, but also many short trans-membrane subunits (sTMs) that are implicated in the proper assembly of complexes. Here we identify a new subunit that we named Stmp1 and have characterized its function using both computational and experimental approaches. Stmp1 is a short trans-membrane protein, and sequence/structure analysis revealed that it shares common features like the small size, presence of a single or two TM region, and a C-terminal charged region, as many typical sTMs of respiratory complexes. Stmp1 is ubiquitously expressed throughout zebrafish embryogenesis. In adults, Stmp1 expression was highest in the brain compared to muscle and liver. In zebrafish larvae (3-5 d.p.f.), antisense morpholino oligonucleotide-mediated knockdown of the Stmp1 gene (Stmp1-MO) resulted in a series of mild morphological defects, including abnormal shape of head and jaw, and cardiac edema. Larvae injected with the Stmp1-MO had negligible responses to touch stimuli. We found that Stmp1-MO injected zebrafish displayed a severe dysfunction of ventilatory activities when exposed to hypoxic conditions. Phylogenetic profiling revealed that all defined respiratory sTMs have restricted or variable phyletic distribution, indicating that they are products of evolutionary innovations to fulfill lineage-related functional requirements for respiratory complexes. Thus, being present in animals, filasterea, choanoflagellida, amoebozoa, and plants, Stmp1 may have evolved to confer a new or complementary regulation of respiratory activities.