Temperature is important environmental information for biological reaction. Animals have acclimation mechanism to environmental temperature changes. We are studying cold acclimation and cold tolerance of nematode C. elegans to reveal how animals respond and acclimate to temperature (Ohta et al., Nature commun, 2014; Okahata et al., Scienceadvances, 2019; Takagaki et al, EMBO rep, 2020). Cold tolerance is a phenomenon that 25 degrees-cultivated wild-type animals can not survive at 2 degrees, whereas 15 degrees-cultivated wild-type can survive at 2 degrees. Additionally, 25 degree-cultivated wild-type is transferred to 15 degrees and stayed for 3 hours, they can survive at 2 degrees. This phenomenon is defined as cold acclimation (Ohta et al., Nature commun, 2014). We show here that HACD-1 has a role to regulate cold acclimation. HACD-1 protein is homologous to human 3-hydroxyacyl-CoenzymeA dehydrogenase (HADH) that catalyzes a beta oxidation reaction of the fatty acid metabolism in mitochondrial matrix. When 15 degree-cultivated
hacd-1 mutant animals are transferred to 25 degrees and stayed for 3 hours,
hacd-1 mutant showed abnormality of increasing survival rate of cold acclimation relative to wild-type.. HACD-1::GFP driven by
hacd-1 promoter were observed in several head neurons and intestine. We expressed
hacd-1 cDNA in intestine and/or almost all neurons of
hacd-1 mutant. The abnormal cold acclimation of
hacd-1 mutant was rescued by expressing
hacd-1 cDNA in almost all neurons, but not in intestine. HACD1 expression in approximately 70 neuron pairs including essential neurons for cold acclimation such as thermosensory neurons (ASJ, ADL and ASG) and their interneurons (AIN and AVJ) driven by multiple neuron promoter also rescued abnormal cold acclimation of the hacd1mutants. To determine the neuron type required for hacd1dependent cold acclimation, we are introducing a series of cellspecific rescue experiments. Since human HADH acts in fatty acid metabolism of mitochondrial matrix, neuronal HACD-1 could play a similar role in the metabolism of mitochondria, which maybe essential for cold acclimation. As ongoing progress, we are trying to measure a temperature of mitochondria in
hacd-1 mutant and wild-type by using genetically encoded temperature indicator tsGFP, to determine a relationship between mitochondria temperature and animal cold acclimation.