Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.

Background: Many common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies.

Natural variation in starvation sensitivity maps to a point mutation in phospholipase IPLA2-VIA in .

Resistance to starvation is a classic complex trait, where genetic and environmental variables can greatly modify an animal's ability to survive without nutrients. In this study, we investigate the genetic basis of starvation resistance using complementary quantitative and classical genetic mapping in . Using the Drosophila Genetics Reference Panel (DGRP) as a starting point, we queried the genetic basis of starvation sensitivity in one of the most sensitive DGRP lines.

Mitochondrial genotype alters the impact of rapamycin on the transcriptional response to nutrients in Drosophila.

Background: In addition to their well characterized role in cellular energy production, new evidence has revealed the involvement of mitochondria in diverse signaling pathways that regulate a broad array of cellular functions. The mitochondrial genome (mtDNA) encodes essential components of the oxidative phosphorylation (OXPHOS) pathway whose expression must be coordinated with the components transcribed from the nuclear genome. Mitochondrial dysfunction is associated with disorders including cancer and neurodegenerative diseases, yet the role of the complex interactions between the mitochondrial and nuclear genomes are poorly understood.