Interaction Between Mitochondria and Sarcoplasmic Reticulum in Airway Smooth Muscle

The Mayo Clinic Cell and Regenerative Physiology Laboratory is exploring the inflammation in reactive oxidant species (ROS) formation and the accumulation of unfolded or damaged proteins that triggers a homeostatic process called the endoplasmic reticulum (ER) stress response.

The ER 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 that, in turn, trigger responses such as contraction that require energy in the form of adenosine triphosphate (ATP). Mitochondria provide ATP, and the elevation of cytoplasmic calcium is coupled to mitochondrial ATP 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 muscle (airway, diaphragm and cardiac muscle) and in motor neurons. They are particularly interested in the effects of inflammation and proinflammatory cytokines on excitation-energy coupling. The lab hypothesizes that ER-mitochondrial interactions represent a complex physiological signaling cascade that underlies a variety of pathophysiologies.