PMID- 34436502 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210831 IS - 2218-1989 (Print) IS - 2218-1989 (Electronic) IS - 2218-1989 (Linking) VI - 11 IP - 8 DP - 2021 Aug 23 TI - Cytoskeletal Arrest: An Anoxia Tolerance Mechanism. LID - 10.3390/metabo11080561 [doi] LID - 561 AB - Polymerization of actin filaments and microtubules constitutes a ubiquitous demand for cellular adenosine-5'-triphosphate (ATP) and guanosine-5'-triphosphate (GTP). In anoxia-tolerant animals, ATP consumption is minimized during overwintering conditions, but little is known about the role of cell structure in anoxia tolerance. Studies of overwintering mammals have revealed that microtubule stability in neurites is reduced at low temperature, resulting in withdrawal of neurites and reduced abundance of excitatory synapses. Literature for turtles is consistent with a similar downregulation of peripheral cytoskeletal activity in brain and liver during anoxic overwintering. Downregulation of actin dynamics, as well as modification to microtubule organization, may play vital roles in facilitating anoxia tolerance. Mitochondrial calcium release occurs during anoxia in turtle neurons, and subsequent activation of calcium-binding proteins likely regulates cytoskeletal stability. Production of reactive oxygen species (ROS) formation can lead to catastrophic cytoskeletal damage during overwintering and ROS production can be regulated by the dynamics of mitochondrial interconnectivity. Therefore, suppression of ROS formation is likely an important aspect of cytoskeletal arrest. Furthermore, gasotransmitters can regulate ROS levels, as well as cytoskeletal contractility and rearrangement. In this review we will explore the energetic costs of cytoskeletal activity, the cellular mechanisms regulating it, and the potential for cytoskeletal arrest being an important mechanism permitting long-term anoxia survival in anoxia-tolerant species, such as the western painted turtle and goldfish. FAU - Myrka, Alexander AU - Myrka A AUID- ORCID: 0000-0002-1056-6839 AD - Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada. FAU - Buck, Leslie AU - Buck L AD - Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada. AD - Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON M5S 3G5, Canada. LA - eng GR - 458021/Natural Sciences and Engineering Research Council of Canada/ PT - Journal Article PT - Review DEP - 20210823 PL - Switzerland TA - Metabolites JT - Metabolites JID - 101578790 PMC - PMC8401981 OTO - NOTNLM OT - ROS OT - actin OT - anoxia OT - calcium OT - gasotransmitters OT - mitochondria OT - mitochondrial membrane potential OT - temperature OT - tubulin OT - western painted turtle COIS- The authors declare no conflict of interest. The funders had no role in the writing of the manuscript. EDAT- 2021/08/27 06:00 MHDA- 2021/08/27 06:01 PMCR- 2021/08/23 CRDT- 2021/08/26 12:26 PHST- 2021/06/30 00:00 [received] PHST- 2021/08/13 00:00 [revised] PHST- 2021/08/14 00:00 [accepted] PHST- 2021/08/26 12:26 [entrez] PHST- 2021/08/27 06:00 [pubmed] PHST- 2021/08/27 06:01 [medline] PHST- 2021/08/23 00:00 [pmc-release] AID - metabo11080561 [pii] AID - metabolites-11-00561 [pii] AID - 10.3390/metabo11080561 [doi] PST - epublish SO - Metabolites. 2021 Aug 23;11(8):561. doi: 10.3390/metabo11080561.