Some animals are able to survive for long time under conditions of drastically reduced oxidative metabolism, called metabolic depression. The most investigated type of the metabolic depression is hibernation. Research into the basic properties of liver mitochondria energetics during hibernation is essential for fundamental biology and medicine. However, the absence of the suitable hepatocyte culture makes it impossible to study the characteristic features of mitochondrial metabolic states in living cells during hibernation. We proposed that under selected conditions, the unicellular eukaryote Tetrahymena pyriformis resembles hepatocytes under hibernation, as (i) both cell types survive under condition of restricted food supply, hypoxia, and accumulation of toxic products of metabolism; (ii) the mechanisms for survival during drastically reduced oxidative metabolism probably developed in the ancestors of the eukaryote mitochondria and may be conserved, in somewhat modified forms, in mitochondria of the ciliates and mammalian cells; (iii) mitochondria isolated from rat liver and Tetrahymena pyriformis are similar in their energetics properties The already published results of experiments with Tetrahymena pyriformis and with mitochondria isolated from the liver of hibernating animals are considered. In this paper to support and develop this suggestion. Sharp decrease in the maximal uncoupler-stimulated respiration rates in liver mitochondria isolated from the hibernating animals was described in many publications. The respiration recordings and Mito Tracker Red fluorescence observations in the ciliates were tentatively explained by low ∆Ψ and high ∆pH. Prior to this study the strong decline in ∆Ψ and the subsequent remodeling of mitochondria into the condensed configuration was found during earlier apoptosis induced by suppression of the respiratory activity. On the grounds of these and other data, a hypothesis is put forward that the prerequisite for reducing the oxidative metabolism and mitochondrial transition to hibernation resembles the early apoptosis, with initial ∆Ψ decline with following mitochondrial matrix transition to a condense configuration. Correct comparison of ∆Ψ of mitochondria isolated from liver of the active and hibernating animals is difficult as probably they have different matrix volumes and energy-independent binding with the ∆Ψ probes.