Mammalian hibernation. Transcriptional and translational controls.

Mammalian hibernation is an amazing strategy for winter survival. Animals sink into a deep torpor where metabolic rate is < 5% of normal, body temperature falls to 0-5 degrees C, and physiological functions are strongly suppressed. Hibernation is a closely regulated process that includes multiple controls on gene transcription and protein translation, the primary subjects of this review. Recent studies by our lab and others have used multiple techniques of gene discovery, including cDNA array screening, to identify genes that are up-regulated in hibernation and continuing studies are tracing the functions of the encoded proteins and the signal transduction systems that regulate expression. For example, up-regulation of fatty acid binding proteins during hibernation facilitates the switch to a primary dependence on lipid fuels by nearly all organs and new studies have shown that up-regulation is mediated by the PPARgamma transcription factor and its co-activator, PGC-1. Several hypoxia-related genes including HIF-1alpha are also up-regulated during hibernation suggesting a role for this transcription factor in mediating adaptive responses for hibernation. Controls on mRNA translation during hibernation accomplish two goals: a general strong suppression of protein synthesis that contributes to energy savings and the selected synthesis of a few specific proteins. These goals are accomplished by mechanisms that include reversible phosphorylation controls on ribosomal initiation and elongation factors and differential distribution of individual mRNA species between polysome and monosome fractions. Studies of gene expression, protein synthesis regulation, controls on fuel metabolism, and signal transduction pathways are combining to produce an integrated model of the biochemical regulation of hibernation.