Figure 5. Schematic diagram of potential SIRT3 action in the skeletal myocyte.

Collectively, our data support a working model in which SIRT3 responds dynamically to various nutritional and physiological signals to potentially impact muscle energy homeostasis via AMPK and PGC-1α. Since AMPK can also phosphorylate and activate CREB [52], SIRT3 may activate CREB directly or through AMPK. Given its dynamic role, SIRT3 action within the skeletal muscle cells may serve as an important diagnostic and therapeutic target for impacting human health and disease.