Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death

Over recent years, it has become clear that mitochondria play a central rol e in many key aspects of animal physiology and pathophysiology. Their centr al and ubiquitous task is clearly the production of ATP. Nevertheless, they also play subtle roles in glucose homeostasis, acting as the sensor for su bstrate supply in the transduction pathway that promotes insulin secretion by the pancreatic beta-cell and that modulates the excitability of the hypo thalamic glucose-sensitive neurons involved in appetite control. Mitochondr ia may also act as sensors of availability of oxygen, the other major mitoc hondrial substrate, in the regulation of respiration. Mitochondria take up calcium, and the high capacity mitochondrial calcium uptake pathway provide s a mechanism that couples energy demand to increased ATP production throug h the calcium-dependent upregulation of mitochondrial enzyme activity. Mito chondrial calcium accumulation may also have a substantial impact on the sp atiotemporal dynamics of cellular calcium signals, with subtle differences of detail in different cell types. Recent work has also revealed the centra lity of mitochondrial dysfunction as an irreversible step in the pathway to both necrotic and apoptotic cell death. This review looks at recent develo pments in these rapidly evolving areas of cell physiology in an attempt to draw together disparate areas of research into it common theme.