Ceramide transfer protein function is essential for normal oxidative stress response and lifespan

Prior research has shown that ceramide transfer protein (CERT) regulates sphingolipid levels in mammalian cells. It was already known that CERT transports ceramide between organelles. However, the role of CERT in whole-animal physiology remains unclear. No prior work had resolved how CERT function affects organismal development. This gap motivated studies using model organisms. Drosophila provides a useful system for studying metabolic pathways. The connection between sphingolipids and oxidative stress is poorly understood. This uncertainty drove investigations into CERT's physiological role.

The aim was to determine how CERT function affects animal physiology. Researchers focused on Drosophila as a model system. They sought to understand the consequences of CERT deficiency. The study targeted oxidative stress and lifespan regulation. They hypothesized that CERT maintains sphingolipid balance. The researchers proposed that sphingolipids protect against oxidative damage. They aimed to test whether CERT is required for normal aging. The study sought to link lipid metabolism to cellular stress resistance.

Scientists used chemical mutagenesis to create Drosophila mutants. They screened for CERT-deficient flies using Western blot analysis. The study measured ceramide levels in mutant and control flies. Researchers assessed membrane fluidity using fluorescent probes. They quantified oxidative damage to cellular proteins. The team tested thermal tolerance under controlled conditions. They monitored lifespan by tracking fly mortality. The study combined biochemical assays with physiological measurements.

Mutant flies lacking CERT died 10-30 days versus 75-90 days for controls. Ceramide phosphoethanolamine levels dropped by >70% in mutants. Ceramide levels also decreased significantly in Dcert flies. Plasma membrane fluidity increased in the absence of CERT. The flies showed heightened susceptibility to reactive oxygen species. Oxidative damage to proteins increased in mutant flies. Thermal tolerance decreased with age in the mutants. ATP levels dropped while glucose increased in the affected flies.

The authors propose that CERT maintains sphingolipid levels necessary for viability. They suggest that ceramide phosphoethanolamine prevents oxidative damage. The study shows that CERT function is required for normal lifespan. The researchers indicate that sphingolipids regulate membrane fluidity. They report that loss of CERT leads to premature aging signs. The findings suggest that sphingolipids protect against oxidative stress. The authors state that CERT function is essential for stress resistance. They conclude that sphingolipid homeostasis is critical for organismal health.