Fig. 1. ATP turnover of cells as a function of time exposed to anoxia or hypothermia. The main figure shows the debilitating cascade of events leading to necrotic cell death. When cellular ATP demand exceeds ATP supply, this cascade is the same (in general if not in specific detail) whether the cells are ‘anoxia- or cold-sensitive’ or ‘anoxia- or cold-tolerant’. The inset shows that a regulated suppression of ATP turnover (i.e. a regulated hypometabolism in which ATP demand balances ATP supply) extends the time to the onset of the debilitating cascade in ‘anoxia- and cold-tolerant cells’. In contrast, an early mismatch between ATP supply and demand in ‘anoxia- and cold-sensitive cells’ leads to a forced hypometabolism which is, in effect, early metabolic failure. Mito, mitochondria; ER, endoplasmic reticulum.