Biliverdin reductase-A is a key modulator in insulin signaling and metabolism
Antonella Tramutola, Fabio Di Domenico, Marzia Perluigi, Eugenio Barone
Abstract
Biliverdin reductase-A (BVRA) is a pleiotropic enzyme traditionally known for its antioxidant role in the heme degradation pathway. Recent findings have redefined BVRA as a master regulator of insulin signaling, acting as a kinase, scaffold, and redox-sensitive integrator of metabolic cues. BVRA modulates key nodes of the insulin cascade and sustains mitochondrial and synaptic function. Notably, BVRA loss precedes the accumulation of canonical markers of insulin resistance both peripherally and in the brain. Here we discuss how BVRA could represent an early cross-tissue biomarker of metabolic vulnerability. Its dysfunction contributes to mitochondrial stress, impaired proteostasis, and cognitive decline, thus linking metabolic and neurodegenerative disorders.