Interaction between mitochondia and sarcoplasmic reticulum in airway smooth muscle

The Cell and Regenerative Physiology Lab is exploring inflammation in reactive oxidant species formation and the accumulation of unfolded or damaged proteins that trigger a homeostatic process. This process is called the endoplasmic reticulum stress response.

The endoplasmic reticulum is important for a number of cellular functions, including the release of stored calcium into the cytoplasm. In muscle fibers and neurons, excitation initiates signaling cascades that involve transient increases in cytoplasmic calcium. In turn, that triggers responses such as contractions that require energy in the form of adenosine triphosphate. Mitochondria provide adenosine triphosphate. The elevation of cytoplasmic calcium is coupled to mitochondrial adenosine triphosphate production through a process of excitation and energy coupling that involves calcium influx into mitochondria.

Researchers in Dr. Sieck's lab are characterizing the basic mechanisms underlying this excitation-energy coupling in airway, diaphragm and cardiac muscles and in motor neurons. They are particularly interested in the effects of inflammation and proinflammatory cytokines on excitation-energy coupling. The lab hypothesizes that endoplasmic reticulum-mitochondrial interactions represent a complex physiological signaling cascade that underlies a variety of pathophysiologies.