A. Hasan and B.E. Staveley*
Published September 12, 2024
Genet. Mol. Res. 23 (3): gmr2350
DOI http://dx.doi.org/10.4238/gmr2350

About the Authors
A. Hasan and B.E. Staveley*

Corresponding author: 
Brian E. Staveley
E-mail: bestave@mun.ca

ABSTRACT

Known for tumor-suppression transcriptional regulation activities, the Retinoblastoma (Rb or Rbf in flies) protein plays a crucial role in cell-cycle regulation and apoptosis. More recently, an established a cytosolic role and mitochondrial localization, the Rb protein seems to cooperate with Drp1 to regulate mitochondrial quality in a transcriptionindependent manner. Control of mitochondrial quality is vital for the assurance of cell survival, and the failure of this function may result in catastrophic mitochondrial dysfunction and cell death. Here we exploited the UAS-Gal4 expression system to direct expression in neurons via the Ddc-Gal4 directing transgene. The directed expression of Drp1 in neuronal populations that include the dopaminergic (DA) neurons under the control of the Ddc-Gal4 transgene can produce a robust Drosophila model of Parkinson Disease (PD) with a severely reduced median lifespan and premature locomotor dysfunction. These are significantly suppressed when Rbf is also overexpressed. Intriguingly, the co-expression of Drp1-RNAi and Rbf-RNAi can restore aging defects associated with Rbf loss of function. A delicate balance between Rbf and Drp activities, to benefit the health of the mitochondrial network, seems to be essential during aging.

Key words: Drosophila melanogaster; aging; climbing ability; mitochondria; Drosophila model of Parkinson disease; Rbf; Drp1