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

Abstract

Metabolic organs 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 organ using Drosophila oenocytes, polyploid hepatocyte-like cells, as a tractable in vivo model. Using 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 controlled by the steroid hormone ecdysone. We further identify the ecdysone-induced nuclear receptor E75 as a key regulator of the timing of cell death, 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 specialised polyploid cells and establishes oenocytes as a powerful in vivo system for studying cell death in metabolic organs.