Suppression Of Autophagy-related Gene Causes Locomotive Defects In Drosophila

Autophagy is one of the two major systems for intracellular protein degradation in which long-life proteins and damaged organelles are sequestered into autophagic vesicles and subsequently degraded via fusion with lysosomes.Objective:Early reports suggest that autophagy contribute to pathogenesis of neurodegenerative diseases such as Alzheimer Disease, Parkinson's Disease and Huntington Disease. However roles of autophagy in regulating neurodegeneration remain largely unknown. In mice, targeted inactivation of autophagy-related genes Atg5 and Atg7 in neurons individually causes abnormal behavior, shorten life-span, neuronal loss and appearance of ubiquitin-positive aggregates in survival neurons.Method:As a model, Drosophila have been widely used in studying of autophagy and neurodegenerative diseases. To understanding the role of autophagy in the pathogenesis of neurodegenerative diseases, we suppressed the expression of Atg5 and Atgl2 individually in Drosophila neurons.Results:The results show that suppression of Atg5 or Atgl2 in neuron resulting similar pathological phenotypes in Drosophila, including: 1) wing developmental defects and abnormal wing posture, fall-down wings; 2) shorten life-span and smaller body size; 3) impaired climbing ability; 4)mitochondrial cristae loss and mitochondrial vacuolation in indirect flight muscle.Conclusion:All these phenotypes suggesting that suppression of autophagy is linked to the molecular pathological mechanism of neurodegenerative disease. Progressive loss of dopaminergic (DA) neurons is one of the pathological hallmarks of PD. However we did not observe obvious loss of the dopaminergic neurons in our Drosophila model, suggesting that the underlying molecular mechanism of pathological phenotype caused by suppression of autophagy-related gene in Drosophila neurons is independent of neuronal death. The fine mechanism of this regulating remains to be further investigate.