Mr. Duchen, Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death, J PHYSL LON, 516(1), 1999, pp. 1-17
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.