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Glucocorticoid receptors modulate mitochondrial function: A novel mechanism for neuroprotection

Jing Du, Bruce McEwen and Husseini K. Manji

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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.

Du J, Wang Y, Hunter R, Wei Y, Blumenthal R, Falke C, Khairova R, Zhou R, Yuan P, Machado-Vieira R, McEwen BS, Manji HK. Dynamic regulation of mitochondrial function by glucocorticoids. Proc Natl Acad Sci USA 2009 Mar 3;106(9):3543-8. Epub 2009 Feb 6.

Authors

Jing Du Corresponding author: duj@mail.nih.gov

National Institute of Mental Health; National Institutes of Health; Bethesda, MD, USA

Bruce McEwen

The Rockefeller University

Husseini K. Manji

Johnson & Johnson Pharmaceutical Research & Development, LLC

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.