3.D.4.11.2
Three subunit cytochrome c oxidase including subunits I (524 aas and 13 TMSs in a 1 + (2)⁶ TMS arrangement); II (232 aas and 3 - 5 TMSs in a 2 TMSs (N-terminal) + 1 - 3 TMSs (C-terminal) arrangement), and III (256 aas and 7 TMSs about equally spaced).  It is a biological temperature-sensing electrical regulator of the devil worm, Halicephalobus mephisto (Guerin et al. 2024). This extremophile metazoan was isolated 1.3 km underground in a South African goldmine, where it adapted to heat and potentially to hypoxia, making its mitochondrial sequence a likely target of adaptational change. The complete mitochondrial genome sequence of this organism was obtained, and it showed through dN/dS analysis evidence of positive selection in H. mephisto cytochrome c oxidase subunits. Seventeen of the positively selected amino acid substitutions were located in proximity to the H- and K-pathway proton channels of the complex. The H. mephisto cytochrome c oxidase completely shuts down at low temperatures (20 °C), leading to a 4.8-fold reduction in the transmembrane proton gradient (ΔΨ_m) compared to the optimal temperature (37 °C). Direct measurement of oxygen consumption found a corresponding 4.6-fold drop at 20 °C compared to 37 °C. Correspondingly, the lifecycle of H. mephisto takes four times longer at low temperature than at higher. This elegant evolutionary adaptation creates a finely-tuned mitochondrial temperature sensor, allowing this ectothermic organism to maximize its reproductive success across varying environmental temperatures (Guerin et al. 2024).