Hepatocyte-like cells die via steroid hormone and nuclear receptor E75-mediated apoptosis

Metabolic tissues must sustain physiological function while retaining the capacity for timely cell death. Systemic hormones play a key role in coordinating this balance, yet how they regulate cell death in vivo remains unclear. Here, we investigate hormone-regulated cell death in a metabolically specialised tissue using Drosophila hepatocyte-like cells, known as oenocytes, as a tractable in vivo model. Through non-invasive longitudinal live imaging combined with oenocyte-specific genetic manipulation, we directly visualise larval oenocyte death during metamorphosis. We show that larval oenocyte loss is a dynamic, multistep process that is controlled by the steroid hormone ecdysone. We further identify the ecdysone-induced nuclear receptor E75 as a key regulator of cell death timing, as loss of E75 triggers premature oenocyte death. Oenocyte-specific manipulation of cell death pathways, together with live imaging using genetically encoded caspase reporters, provides direct evidence that larval oenocytes die by apoptosis. Together, this work defines how systemic hormonal signals regulate the timing of apoptosis in metabolically active cells, and establishes oenocytes as a powerful in vivo system for studying metabolic cell death.