Glucocorticoid receptors modulate mitochondrial function

Abstract

It has become increasingly clear that glucocorticoid (GC) signaling not only comprises classic nuclear receptor binding—that is, glucocorticoid receptors (GRs) to their response element in the nucleus—but also involves rapid, non-genomic efforts to regulate signaling cascades and other cell functions in the cytoplasm as well as other cell organelles. In a recent study, we found that GRs form a complex with B-cell lymphoma 2 (Bcl-2), translocate to mitochondria in response to corticosterone (CORT), and modulate mitochondrial calcium and oxidation in an inverted U–shaped manner. It is also well-established that steroid and thyroid hormone receptors regulate mitochondrial function to protect cells against various challenges and modulate synaptic plasticity. Here, we explore how such work reveals a fundamental mechanism whereby GCs regulate mitochondrial functions, and provides a mechanistic basis for therapeutic methods to rescue mitochondrial dysfunction during chronic stress or related psychiatric and neurodegenerative disorders.