UASt regulatory sequences drive expression of an inverted repeat.
Expression of tamKK100485 under the control of Scer\GAL4bam.T:Hsim\VP16 prevents the elimination of mitochondrial nucleoids (containing the mtDNA) in developing spermatids.
Expression of tamKK100485 under the control of Scer\GAL4Act5C.PU results in reduced complex I activity and ATP levels compared with controls. Flies have a significantly shortened lifespan compared to controls.
Flies expressing tamKK100485 under the control of Scer\GAL4tub.PU (limited to the adult stages using Scer\GAL80ts.αTub84B) have a significantly shortened lifespan compared to controls.
Flies expressing tamKK100485 in cholinergic neurons under the control of Scer\GAL4Cha.7.4 (co-expressed with Dcr-2Scer\UAS.cDa) show an age-related decline in climbing performance similar to controls. Flies do not exhibit any differences in spontaneous activity, speed of walking or total distance traveled. No neuron loss is seen in the brain of these flies.
Flies expressing tamKK100485 in dopaminergic neurons under the control of Scer\GAL4ple.PF (co-expressed with Dcr-2Scer\UAS.cDa) show a significant and progressive age-related decline in climbing performance when compared with controls. These flies have a normal lifespan but show decreased activity and, when moving, they walk at a slower speed and cover less distance compared with controls. Expression under the control of Scer\GAL4ple.PF results in a significant and age-related decrease in dopaminergic neurons. PPL1 and PPM1/2 dopaminergic neuron clusters show progressive loss of neurons from 31 to 70 days, whereas PPM3 and PAL clusters show significant early loss( at 31 days) but no significant difference is seen with age.
When compared with age-matched controls, flies expressing tamKK100485 in serotonergic neurons under the control of Scer\GAL4Trh.PB (co-expressed with Dcr-2Scer\UAS.cDa) do not show decreased climbing performance. A small but significantly significant reduction in activity is seen in aged flies. Serotonergic neuron loss is seen only in aged flies. No neuron loss is seen at 5 days, but significant loss is present by 31 days.
A significant loss of dopaminergic neurons, but not serotonergic neurons, is seen in 60 day old flies expressing tamKK100485 under the control of Scer\GAL4elav.PU (co-expressed with Dcr-2Scer\UAS.cDa). Cell loss affects all dopaminergic clusters except PAL.
PolG1KK100485, Scer\GAL4Act5C.PU has partially lethal - majority die phenotype, suppressible | partially by parkUAS.cHa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during larval stage phenotype, suppressible | partially by parkUAS.cHa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during pupal stage phenotype, suppressible | partially by parkUAS.cHa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has partially lethal - majority die phenotype, suppressible | partially by Drp1UAS.cDa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during larval stage phenotype, suppressible | partially by Drp1UAS.cDa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during pupal stage phenotype, suppressible | partially by Drp1UAS.cDa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has partially lethal - majority die phenotype, suppressible | partially by dhdUAS.cUa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during larval stage phenotype, suppressible | partially by dhdUAS.cUa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during pupal stage phenotype, suppressible | partially by dhdUAS.cUa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has partially lethal - majority die phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during larval stage phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during pupal stage phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4ple.PF has abnormal neuroanatomy phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4Act5C.PU has partially lethal - majority die phenotype, suppressible | partially by Scer\NDI1UAS.cSa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during larval stage phenotype, suppressible | partially by Scer\NDI1UAS.cSa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during pupal stage phenotype, suppressible | partially by Scer\NDI1UAS.cSa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4da.PU has increased mortality during development phenotype, non-suppressible by Cint\AOXmut.UAS, Scer\GAL4da.PU
PolG1KK100485, Scer\GAL4da.PU has increased mortality during development phenotype, non-suppressible by Cint\AOXwt.UAS, Scer\GAL4da.PU
PolG1KK100485, Scer\GAL4da.PU has increased mortality during development phenotype, non-suppressible by Cint\AOXUAS.cFa, Scer\GAL4da.PU
PolG1KK100485, Scer\GAL4Act5C.PU has partially lethal - majority die phenotype, non-suppressible by pleUAS.cFa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4Act5C.PU has some die during larval stage phenotype, non-suppressible by pleUAS.cFa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4ple.PF has abnormal neuroanatomy phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4Act5C.PU has some die during pupal stage phenotype, non-suppressible by pleUAS.cFa, Scer\GAL4Act5C.PU
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPL1 neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPL2ab neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPL2c neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPM1 neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPM2 neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPM3 neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PAL neuron phenotype, suppressible by Cint\AOXUAS.cFa, Scer\GAL4ple.PF
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPL1 neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPL2ab neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPL2c neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPM1 neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPM2 neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PPM3 neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
PolG1KK100485, Scer\GAL4ple.PF has dopaminergic PAL neuron phenotype, non-suppressible by Scer\GAL4ple.PF/Scer\NDI1UAS.cSa
Expression of parkScer\UAS.cHa partially suppresses the lethality seen when tamKK100485 is expressed under the control of Scer\GAL4Act5C.PU.
Expression of Drp1Scer\UAS.cDa partially suppresses the lethality seen when tamKK100485 is expressed under the control of Scer\GAL4Act5C.PU.
Expression of dhdScer\UAS.cUa partially suppresses the lethality seen when tamKK100485 is expressed under the control of Scer\GAL4Act5C.PU.
Expression of pleScer\UAS.cFa does not suppress the lethality seen when tamKK100485 is expressed under the control of Scer\GAL4Act5C.PU.
Expression of Scer\NDI1Scer\UAS.cSa partially suppresses the lethality seen when tamKK100485 is expressed under the control of Scer\GAL4Act5C.PU.
Expression of Zzzz\AOXScer\UAS.cFa completely suppresses the lethality seen when tamKK100485 is expressed under the control of Scer\GAL4Act5C.PU. The reduction in total ATP content is also suppressed.
Expression of Zzzz\AOXScer\UAS.cFa completely suppresses the dopaminergic neuron loss seen when tamKK100485 is expressed under the control of Scer\GAL4ple.PF.
PolG1KK100485 is rescued by PolG1UASp.RR.Tag:FLAG/Scer\GAL4VP16.bam
PolG1KK100485 is rescued by PolG1D263A.UASp.RR.Tag:FLAG/Scer\GAL4VP16.bam
PolG1KK100485 is partially rescued by PolG1E813V.UASp.RR.Tag:FLAG/Scer\GAL4VP16.bam
The failure to eliminate mitochondrial nucleoid and mtDNA during spermatid development characteristic for males expressing tamKK100485 under the control of Scer\GAL4bam.T:Hsim\VP16 can be fully rescued by co-expression of either tamUASp.RR.Tag:FLAG or tamD263A.UASp.RR.Tag:FLAG and is partially rescued by co-expression of tamE813V.UASp.RR.Tag:FLAG but the spermatids still retain some nucleoids during late individualization stage.