The Dictyostelium rhomboid proteases and mitochondrial disease

Rhomboid membrane proteases are integral to pathogenicity of several microbial eukaryotes and the role of mitochondrial rhomboids is important in pathologies beyond infectious disease. By virtue of their ability to cleave tethered proteins, this relatively recently discovered protein family have been found to activate substrates, release mobile signals, and progress cell regulatory pathways. The Dictyostelium model microbe allows the study of an evolutionarily ancient set of rhomboids, aberrant expression of which affects phagocytosis, response to chemoattractants, phototaxis, growth and cell size, ATP levels, and mitochondrial ultrastructure. We report the particularly mitochondrial focus of rhomboids in this amoeba and consider the relevance of this beyond the model organism, given the central role of the human mitochondrial rhomboid in mitophagy, ageing and neurodegenerative disease.