Warm up and cool down!

In adaption to shifts in ambient temperature, both prokaryotic and eukaryotic cells maintain physiological homeostasis by adjusting various cellular properties, including membrane lipid fluidity, the capacity to maintain proteostasis and rate of protein synthesis [1]. How cells respond to temperature changes is a fundamental question in cell physiology. Here we briefly review current understanding of cellular adaptation to temperature shifts, focusing on our recent findings of homeostatic membrane fluidity regulation by the EGL-25/ACDH-11 pathway in C. elegans [2]. Several molecular sensors that transduce temperature shifts to cellular homeostatic responses have been previously described. Heat shock factor (HSF) is an evolutionarily conserved master regulator of heat shock-induced transcription. HSF is normally sequestered by cytoplasmic chaperon proteins and remains inactive. To alleviate protein mis-folding and subsequent aggregation upon heat stress, heat shock chaperon proteins bind to mis-folded proteins and dissociate from HSF. This allows HSF to translocate to the cell nucleus and activate transcription by binding to DNA regulatory elements to promote proteostasis and thermotolerance. Exposure to cold temperature also profoundly affects organismal physiology. For example, hypothermia protects cells against cellular oxidative injuries. Unlike the well-studied HSF pathway, how cold is sensed and transduced to downstream effectors remains poorly defined. In addition, molecules specifically present in thermosensory neurons can also sense temperature changes. The best-known molecular thermoreceptors are conserved members of the transient receptor potential (TRP) family of cation channels. For example, in mammals, TRPV1-4 and TRPM8 channels sense heat and cold, respectively. In C. elegans, TRPA-1 senses cold and mediates cold-induced extension of lifespan [3]. Because temperature shifts thermodynamically alter membrane fluidity in a nonspecific manner, cells must maintain membrane fluidity homeostasis upon shifts in temperature. Low temperature decreases the fluidity of the cytoplasmic membrane, which triggers upregulation of lipid desaturases to convert saturated fatty acids into unsaturated fatty acids to increase membrane fluidity [4]. This fundamental process of maintaining normal ranges of membrane fluidity is called homeoviscous adaptation (HVA). HVA occurs in single-celled as well as multicellular organisms. However, mechanisms for HVA in eukaryotes have been unknown. From a C. elegans genetic screen exploring how genes control sensitivity to oxygen, Ma et al. discovered a novel pathway comprising the genes egl-25 (or paqr-2, a homolog of mammalian adiponectin receptors) and acdh-11 (acyl-CoA dehydrogenase, ACDH) that promote temperature adaptation via a stearoyl-CoA desaturase, FAT-7. C. elegans survives and reproduces optimally in temperatures ranging from 15°C to 25°C; this requires membrane fluidity …