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Updated: Apr 19, 2026
Measurement of Lifespan in Drosophila melanogaster
Published on: January 7, 2013
A Drosophila ABC transporter regulates lifespan
He Huang1, Ying Lu-Bo1, Gabriel G Haddad2
1Department of Pediatrics (Division of Respiratory Medicine), University of California San Diego, La Jolla, California, United States of America.
Abstract:
MRP4 (multidrug resistance-associated protein 4) is a member of the MRP/ABCC subfamily of ATP-binding cassette (ABC) transporters that are essential for many cellular processes requiring the transport of substrates across cell membranes. Although MRP4 has been implicated as a detoxification protein by transport of structurally diverse endogenous and xenobiotic compounds, including antivirus and anticancer drugs, that usually induce oxidative stress in cells, its in vivo biological function remains unknown. In this study, we investigate the biological functions of a Drosophila homolog of human MRP4, dMRP4. We show that dMRP4 expression is elevated in response to oxidative stress (paraquat, hydrogen peroxide and hyperoxia) in Drosophila. Flies lacking dMRP4 have a shortened lifespan under both oxidative and normal conditions. Overexpression of dMRP4, on the other hand, is sufficient to increase oxidative stress resistance and extend lifespan. By genetic manipulations, we demonstrate that dMRP4 is required for JNK (c-Jun NH2-terminal kinase) activation during paraquat challenge and for basal transcription of some JNK target genes under normal condition. We show that impaired JNK signaling is an important cause for major defects associated with dMRP4 mutations, suggesting that dMRP4 regulates lifespan by modulating the expression of a set of genes related to both oxidative resistance and aging, at least in part, through JNK signaling.
Insights
The multidrug resistance-associated protein 4 (MRP4) transporter regulates lifespan and oxidative stress resistance in Drosophila. Its absence shortens lifespan, while its presence extends it by modulating JNK signaling.
Area of Science:
- Cellular Biology
- Genetics
- Biochemistry
Background:
- Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette (ABC) transporter involved in cellular detoxification.
- MRP4 transports diverse compounds, including drugs, and is linked to oxidative stress, but its in vivo function is unclear.
- Investigating Drosophila MRP4 (dMRP4) offers insights into conserved biological roles.
Purpose of the Study:
- To elucidate the in vivo biological functions of dMRP4 in Drosophila.
- To determine the role of dMRP4 in response to oxidative stress and its impact on lifespan.
- To explore the molecular mechanisms, including JNK signaling, by which dMRP4 influences aging and stress resistance.
Main Methods:
- Examined dMRP4 expression under oxidative stress conditions (paraquat, hydrogen peroxide, hyperoxia).
- Assessed lifespan and oxidative stress resistance in dMRP4 knockout and overexpression Drosophila models.
- Utilized genetic manipulations to investigate dMRP4's role in JNK (c-Jun NH2-terminal kinase) signaling pathways.
Main Results:
- dMRP4 expression increases under oxidative stress in Drosophila.
- Flies lacking dMRP4 exhibit reduced lifespan under both normal and oxidative stress conditions.
- Overexpression of dMRP4 enhances oxidative stress resistance and extends lifespan.
- dMRP4 is essential for JNK activation during oxidative stress and basal transcription of JNK target genes.
- Impaired JNK signaling in dMRP4 mutants contributes to lifespan defects.
Conclusions:
- dMRP4 plays a critical role in regulating lifespan and oxidative stress resistance in Drosophila.
- dMRP4 modulates lifespan, at least partly, through the JNK signaling pathway.
- These findings highlight dMRP4 as a key regulator of aging and stress response, with potential implications for human health.
