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Background  Mitochondrial porin, also known as the voltage-dependent anion channel (VDAC), is a multi-functional channel protein that shuttles metabolites between the mitochondria and the cytosol and implicated in cellular life and death decisions. The inhibition of  porin  under the control of neuronal  Ddc-Gal4  result in short lifespan and in an age-dependent loss in locomotor function, phenotypes that are strongly associated with Drosophila models of Parkinson disease.    Methods  Loss of  porin  function was achieved through exploitation of RNA interference while derivative lines were generated by homologous recombination and tested by PCR. The  UAS/Gal4  expression system was exploited with directed expression in neurons achieved with the use of the  Dopa decarboxylase  and in the developing eye with the  Glass multiple reporter  transgenes. Statistical analyses for ageing assay employed Log rank (Mantel-Cox) test, climbing indices were fitted with a non-linear curve and confidence intervals compared at 95%. Biometric analysis of the eye phenotypes was obtained by unpaired student  T -test.    Results  The expression of  α-synuclein  in neuronal populations that include dopamine producing neurons under the control of  Ddc-Gal4  produces a robust Parkinson disease model, and results in severely reduced lifespan and locomotor dysfunction. In addition, the  porin -induced phenotypes are greatly suppressed when the pro-survival  Bcl-2  homologue  Buffy  is overexpressed in these neurons and in the developing eye adding to the cellular advantages of altered expression of this anti-apoptotic gene. When we co-expressed  α-synuclein  along with  porin , it results in a decrease in lifespan and impaired climbing ability. This enhancement of the  α-synuclein- induced phenotypes observed in neurons was demonstrated in the neuron rich eye, where the simultaneous co-expression of  porin-RNAi  and  α-synuclein  resulted in an enhanced eye phenotype, marked by reduced number of ommatidia and increased disarray of the ommatidia.    Conclusions  The inhibition of  porin  in dopaminergic neurons among others result in reduced lifespan and age-dependent loss in climbing ability, phenotypes that are suppressed by the overexpression of the sole pro-survival  Bcl-2  homologue  Buffy . The inhibition of  porin  phenocopies Parkinson disease phenotypes in Drosophila, while the overexpression of  Buffy  can counteract these phenotypes to improve the overall “healthspan” of the organism.

Loss of porin function in dopaminergic neurons of Drosophila is suppressed by Buffy