Cytoplasmic signaling in the control of mitochondrial uproar?

During times of peace cells are dependent on a balanced crosstalk with their surrounding environment. Survival and proper functioning not only require physical contact with their neighbors, but also depend on a plethora of soluble factors such as hormones or growth factors. The full spectrum of possible cell fates is governed by these mutual and highly dynamic interactions. In the extreme case a dissonance in this "orchestra of life" leads to cell death. However, in order for this to happen a variety of safeguard mechanisms have to fail and cells are normally sufficiently guarded against these threats.Subversion of intracellular control mechanisms is linked to many pathophysiological conditions. In particular, cancer cells are geared towards cellular autonomy, which is achieved through aberrant activation of intracellular signaling processes. As a consequence these cells are in a preemptive way programmed to withstand hostile conditions and to thrive in a growth and survival limiting environment. Thus cancer provided a useful model for the delineation of mechanisms used to counter potential assaults. Its analysis taught us that tumors in a unique way are equipped to withstand limitation in life supporting oxygen or nutrient supply. Many of the genetic defects found in tumors reside in signaling cascades or proteins, supporting the key role of aberrant signaling in this. However, protective mechanisms also can be triggered in a more rapid and transient fashion. During transplantation organs are temporarily deprived of oxygen, nutrients and growth factors (ischemia). A decrease in myocardial oxygen delivery initially results in decreased contractile activity and oxygen consumption, a phenomenon termed hibernating myocardium [1]. Prolonged hypoxia may also reduce ATP demand by down-regulating protein synthesis [2]. Restoration of blood flow (reperfusion) corrects these deficits but at the same time initiates a detrimental cascade, which in the end can lead to irreversi