Preprint Article Version 1 This version is not peer-reviewed

Altered Parkin and Bcl-2 Expression Suppresses Drp1 Gain and Loss of Function Age-Related Phenotypes in Drosophila

Version 1 : Received: 15 July 2024 / Approved: 16 July 2024 / Online: 16 July 2024 (08:27:15 CEST)

How to cite: Hasan, A.; Staveley, B. E. Altered Parkin and Bcl-2 Expression Suppresses Drp1 Gain and Loss of Function Age-Related Phenotypes in Drosophila. Preprints 2024, 2024071258. https://doi.org/10.20944/preprints202407.1258.v1 Hasan, A.; Staveley, B. E. Altered Parkin and Bcl-2 Expression Suppresses Drp1 Gain and Loss of Function Age-Related Phenotypes in Drosophila. Preprints 2024, 2024071258. https://doi.org/10.20944/preprints202407.1258.v1

Abstract

The relationship of Amyotrophic Lateral Sclerosis, Parkinson Disease and other age-related neurodegenerative diseases associated with mitochondrial dysfunction has led to study of the mitochondrial fission gene Drp1 in Drosophila. Drp1 can interact with mitochondrial proteins including parkin and the Drosophila Bcl-2 proteins. Mutations in Drp1 can lead to mitochondrial dysfunction and neuronal loss. Ddc-Gal4 was exploited to direct the expression of Drp1 and the inhibition of Drp1 in neurons. Here, the inhibition of Drp1 seems to compromise locomotor function throughout life but does not alter longevity. The consequences of Drp1 overexpression can be suppressed through overexpression of pro-survival Bcl-2 gene Buffy or by inhibition of the pro-cell death Bcl-2 homologue Debcl. The expression of Buffy suppresses the poor climbing induced by loss of Drp1 function. Interestingly, the loss of parkin function is rescued by the directed inhibition of Drp1. Alteration of the expression of Drp1 acts to phenocopy neurodegenerative disease phenotypes in Drosophila, while overexpression of Buffy can counteract these phenotypes to improve overall health. The pro-survival effect of Buffy can rescue the phenotypic effect due to the Drp1-induced apoptosis. The diminished health due to either overexpression or inhibition of Drp1 has produced a novel model to investigate mechanisms underlying neurodegenerative disease.

Keywords

Drp1; Buffy; Debcl; parkin; Drosophila melanogaster; Amyotrophic Lateral Sclerosis; Parkinson Disease; mitochondrial fission; mitochondrial dysfunction.

Subject

Biology and Life Sciences, Aging

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