Recent advances in thermoregulation

Thermoregulation is the maintenance of a relatively constant core body temperature. Humans normally maintain a body temperature at 37°C, and maintenance of this relatively high temperature is critical to human survival. This concept is so important that control of thermoregulation is often the principal example cited when teaching physiological homeostasis. A basic understanding of the processes underpinning temperature regulation is necessary for all undergraduate students studying biology and biology-related disciplines, and a thorough understanding is necessary for those students in clinical training. Our aim in this review is to broadly present the thermoregulatory process taking into account current advances in this area. First, we summarize the basic concepts of thermoregulation and subsequently assess the physiological responses to heat and cold stress, including vasodilation and vasoconstriction, sweating, nonshivering thermogenesis, piloerection, shivering, and altered behavior. Current research is presented concerning the body's detection of thermal challenge, peripheral and central thermoregulatory control mechanisms, including brown adipose tissue in adult humans and temperature transduction by the relatively recently discovered transient receptor potential channels. Finally, we present an updated understanding of the neuroanatomic circuitry supporting thermoregulation.

Translation suppression promotes stress granule formation and cell survival in response to cold shock

Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2a (eIF2a) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock-induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2a phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia.