Abstract
Caenorhabditis elegans is useful for assessing biological effects of spaceflight and simulated microgravity. The molecular response of organisms to simulated microgravity is still largely unclear. Mitochondrial unfolded protein response (mt UPR) mediates a protective response against toxicity from environmental exposure in nematodes. Using HSP-6 and HSP-60 as markers of mt UPR, we observed a significant activation of mt UPR in simulated microgravity exposed nematodes. The increase in HSP-6 and HSP-60 expression mediated a protective response against toxicity of simulated microgravity. In simulated microgravity treated nematodes, mitochondria-localized ATP-binding cassette protein HAF-1 and homeodomain-containing transcriptional factor DVE-1 regulated the mt UPR activation. In the intestine, a signaling cascade of HAF-1/DVE-1-HSP-6/60 was required for control of toxicity of simulated microgravity. Therefore, our data suggested the important role of mt UPR activation against the toxicity of simulated microgravity in organisms.
Highlights
During the spaceflight, the significant risk on movement, muscle, and metabolism of human beings and animals have been frequently observed[1,2,3,4,5]
Using the transgenic strain of zcIs13[HSP-6::GFP], we found an obvious increase in HSP-6::GFP expression in the intestine of nematodes treated with simulated microgravity (Fig. 1b)
We further found that RNA interference (RNAi) knockdown of haf-1 or dve-1 induced the more severe toxicity of simulated microgravity in inducing intestinal reactive oxygen species (ROS) production and in decreasing locomotion behavior compared with those in wild-type nematodes (Fig. 3b,c), suggesting that the nematodes with RNAi knockdown of haf-1 or dve-1 were susceptible to the toxicity of simulated microgravity
Summary
The significant risk on movement, muscle, and metabolism of human beings and animals have been frequently observed[1,2,3,4,5]. With the work in “the first International C. elegans Experiment in Space” (ICE-First) experiments as an example, it has been observed that microgravity could potentially at least cause the toxicity on early embryogenesis, muscle development, germline development, locomotion behavior, and reproduction in nematodes[17,18,19,20,21,22,23]. The toxicity of simulated microgravity on nematodes could be further assessed more recently[24,25,26,27]. The observed toxicity induced by simulated microgravity was under the control of insulin and p38 mitogen-activated protein kinase (MAPK) signaling pathways in nematodes[24,26]. The response of mt UPR signaling to simulated microgravity remains largely unclear. We here examined the induction of mt UPR in simulated microgravity treated nematodes and the underlying mechanism. Our data demonstrated the noticeable activation of mt UPR in simulated microgravity treated nematodes. The mtUPR signaling was involved in the regulation of response to simulated microgravity
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