University of Pittsburgh

Mitochondria are multi-functional organelles

Mitochondria are considered to have evolved from bacteria that invaded into our ancestor cells about 300 million years ago (endosymbiotic theory). However, mitochondria have now undertaken various functions in the cells, and their existence has become indispensable for our vital activities. In addition to their well-known roles in the ATP production, mitochondria serve critical roles as an intracellular calcium ion store along with the ER, and as a place for the synthesis of intracellular small molecules such as heme, iron-sulfur cluster and steroid hormones. Mitochondria in brown adipose tissue are important for body heat production. Furthermore, for some reason, signal transduction machineries involved in the immune response against viral infection and in the execution of certain types of cell death also exist in mitochondria, and thus mitochondria function as a hub of these intracellular signal transduction pathways.

Mitochondrial stress response

During the process of performing such a variety of functions, mitochondria are constantly exposed to various stresses. For example, ROS, inevitable byproducts of the ATP production, damage mitochondria by oxidizing mitochondrial membrane lipids and proteins. Recent series of research have revealed that mitochondria are equipped with several strategies to cope with these stresses and maintain the quality of mitochondria. These mechanisms are called as “mitochondrial stress response” or \"mitochondrial quality control\". For example, mitophagy is a mechanism that eliminates dysfunctional mitochondria from the cells by autophagy. It has also been found that mitochondria are actively communicating with other intracellular organelles to evoke the proper stress response. For example, the accumulation of abnormal mitochondrial proteins has been shown to be signaled to the nucleus and promotes specific transcriptional program to relieve mitochondrial proteotoxic stress (mtUPR). In order to drive these mitochondrial stress responses, proteins that can monitor the abnormalities in mitochondria and transmit that information to other proteins are necessary. In our laboratory, we are interested in identifying critical molecular players in mitochondrial stress responses and elucidating their roles. Our mission is finding a clue to enhance human health through basic mitochondrial biology research.