Abstract: 【Aim】 The homeostasis of mitochondria is maintained by a wide range of molecular processes in eukaryotic cells. Very recently, microRNAs (miRNAs) are emerging as vital players of mitochondrial homeostasis. However, our understanding of how miRNAs regulate mitochondrial homeostasis is still incomplete. Our study aims to examine the roles and mechanisms of miRNAs in mitochondrial homeostasis regulation. 【Methods】 A gain-of-function screen was performed in Drosophila melanogaster during which miRNAs were over-expressed in the larval fat body cells and the mitochondrial integrity was monitored. The targets of miRNAs were predicted by bioinformatics methods and RNAi knock-down experiments were performed to examine their effects on mitochondrial morphology. 【Results】 A total of 106 miRNAs were screened in larval fat body of D. melanogaster, among which the over-expression of 21 miRNAs resulted in developmental defects of fat body. When over-expressed in the larval fat tissue of D. melanogaster, 10 miRNAs led to lethality at the early larval stage, while the other 11 miRNAs led to pupal lethality. Over-expression of miR-2 was found to result in abnormal aggregation of mitochondria in the larval fat body cells of D. melanogaster. Sequence analysis revealed that the Pink1 gene may be a target of miR-2. The expression level of Pink1 gene was shown to be down-regulated by miR-2 over-expression. Genetic interaction experiments demonstrated that over-expression of Pink1 was sufficient to rescue the abnormal aggregation of mitochondria caused by miR-2. 【Conclusion】 Our data support the view that miR-2 likely targets Pink1 to modulate mitochondrial homeostasis.

Key words: Drosophila melanogaster, miRNA, mitochondria, homeostasis, miR-2, Pink1