Rhomboid-7 over-expression results in Opa1-like processing and malfunctioning mitochondria
2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 414, no 2, 315-320 p.Article in journal (Refereed) Published
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 . 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 Opal-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 Opal-like. Our results suggest that rho-7 and Opal-like function in a common molecular pathway affecting mitochondrial function and apoptosis in Drosophila melanogaster.
Place, publisher, year, edition, pages
2011. Vol. 414, no 2, 315-320 p.
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:sh:diva-14944DOI: 10.1016/j.bbrc.2011.09.047ISI: 000296404800008ScopusID: 2-s2.0-80054841370OAI: oai:DiVA.org:sh-14944DiVA: diva2:483023