title: Rhomboid-7 over-expression results in Opa1-like processing and malfunctioning mitochondria.
abstract: Rhomboid-7 (rho-7) is a mitochondrial-specific intramembranous protease. The loss-of-function mutation rho-7 results in semi-lethality, while escapers have a reduced lifespan with several neurological disorders [1]. Here we show that general, or CNS-specific expression of rho-7 can rescue the lethality of rho-7. General, or CNS-specific over-expression of rho-7 in otherwise wild-type animals caused semi-lethality, with approximately 50% of the animals escaping this lethality, developing into adults displaying a shortened life span with larval locomotory problem. On a cellular level, over-expression resulted in severe depression of ATP levels and cytochrome c oxidase subunit II mRNA levels, a lowered number of mitochondria in neurons and aggregation of mitochondria in the brain indicating mitochondrial malfunction. Over-expression of rho-7 in developing eye discs resulted in an elevated apoptotic index. In the CNS, elevated levels of rho-7 were accompanied by both isoforms of Opa1-like, a dynamin-like GTPase, a mitochondrial component involved in regulating mitochondrial dynamics and function, including apoptosis. Most, but not all, of rho-7 over-expression phenotypes were suppressed by introducing a heterozygous mutation for Opa1-like. Our results suggest that rho-7 and Opa1-like function in a common molecular pathway affecting mitochondrial function and apoptosis in Drosophila melanogaster.
authors.affiliation: Department of Neuroscience, NA4202, MC9111, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9111, USA. mokhlasur.rahman@utsouthwestern.edu
authors.forename: Mokhlasur
authors.initials: M
authors.lastname: Rahman
authors.forename: Per
authors.initials: P
authors.lastname: Kylsten
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C527116:OPA1 protein, Drosophila; C513147:rho-7 protein, Drosophila; D000255:Adenosine Triphosphate; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV