Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster

Karis A. Ederer, Kelly Jin, Sarah Bouslog, Lu Wang, Gregory S. Gorman, Glenn C. Rowe, Peter Abadir, Daniel Raftery, Douglas Moellering, Daniel Promislow, Patricia Jumbo-Lucioni, Maria De Luca

Research output: Contribution to journalArticle

Abstract

The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug's impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

Original languageEnglish (US)
JournalInternational Journal of Molecular Sciences
Volume19
Issue number11
DOIs
StatePublished - Oct 26 2018

Fingerprint

enzyme inhibitors
angiotensins
Lisinopril
Drosophila
Drosophila melanogaster
Angiotensin-Converting Enzyme Inhibitors
Metabolism
Nutrients
Enzymes
Genotype
Oxygen
respiration
nutrients
metabolism
Metabolic Networks and Pathways
Diptera
inhibitors
Reactive Oxygen Species
renin
Respiration

Keywords

  • aging
  • angiotensin-converting enzyme inhibitors
  • genetic background
  • nutrient metabolism
  • nutritional stress

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster. / Ederer, Karis A.; Jin, Kelly; Bouslog, Sarah; Wang, Lu; Gorman, Gregory S.; Rowe, Glenn C.; Abadir, Peter; Raftery, Daniel; Moellering, Douglas; Promislow, Daniel; Jumbo-Lucioni, Patricia; De Luca, Maria.

In: International Journal of Molecular Sciences, Vol. 19, No. 11, 26.10.2018.

Research output: Contribution to journalArticle

Ederer, Karis A. ; Jin, Kelly ; Bouslog, Sarah ; Wang, Lu ; Gorman, Gregory S. ; Rowe, Glenn C. ; Abadir, Peter ; Raftery, Daniel ; Moellering, Douglas ; Promislow, Daniel ; Jumbo-Lucioni, Patricia ; De Luca, Maria. / Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 11.
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