Winter survival for many kinds of animals involves freeze tolerance, the ability to endure the conversion of about 65% of total body water into extracellular
ice and the consequences that freezing imposes including interruption of vital processes (e.g., heartbeat and breathing), cell shrinkage, elevated osmolality,
anoxia/
ischemia, and potential physical damage from
ice. Freeze-tolerant animals include various terrestrially hibernating amphibians and reptiles, many species of insects, and numerous other invertebrates inhabiting both terrestrial and intertidal environments. Well-known strategies of freezing survival include accumulation of low molecular mass
carbohydrate cryoprotectants (e.g.,
glycerol), use of
ice nucleating agents/
proteins for controlled triggering of
ice growth and of
antifreeze proteins that inhibit
ice recrystallization, and good tolerance of
anoxia and
dehydration. The present article focuses on more recent advances in our knowledge of the genes and
proteins that support freeze tolerance and the metabolic regulatory mechanisms involved. Important roles have been identified for
aquaporins and transmembrane channels that move cryoprotectants,
heat shock proteins and other chaperones,
antioxidant defenses, and metabolic rate depression. Genome and
proteome screening has revealed many new potential targets that respond to freezing, in particular implicating cytoskeleton remodeling as a necessary facet of low temperature and/or cell volume adaptation. Key regulatory mechanisms include reversible phosphorylation control of metabolic
enzymes and
microRNA control of gene transcript expression. These help to remodel metabolism to preserve core functions while suppressing energy expensive metabolic activities such as the cell cycle. All of these advances are providing a much more complete picture of life in the frozen state.