Catalase, a heme-containing antioxidant enzyme, was once considered essential for human survival. It is widely distributed in the human body and is particularly abundant in red blood cells. The term “acatalasemia” first appeared in the Proceedings of the Japan Academy in 1951, drawing global attention to families genetically deficient in catalase. This deficiency not only altered the significance of catalase but also played a pioneering role in human genetics during an era of limited genetic methodology. In this article, we examine the discovery of acatalasemia by an otolaryngologist during surgery on an 11-year-old girl. This remarkable journey led to epoch-making research spanning biochemistry, hematology, and human genetics.

Calcium ions (Ca²⁺) play critical roles in various biological phenomena. The free Ca²⁺ concentration in the cytoplasm of a resting cell is at the 10^-7 M level, whereas that outside the cell is 10^-3 M, creating a 10,000-fold gradient of Ca²⁺ concentrations across the cell membrane, separating the intracellular and extracellular solutions.^1),2) When a cell is activated by external stimuli, the intracellular Ca²⁺ concentration increases to levels of 10^-6–10^-5 M through Ca²⁺ entry from the extracellular solution via plasma membrane Ca²⁺ channels and/or Ca²⁺ release from intracellular stores. This transient increase in Ca²⁺ functions as an important signal mediated by Ca²⁺ sensors. Thus, Ca²⁺ signals are transmitted to intracellular loci such as distinct, localized targets of Ca²⁺ sensors. Among numerous Ca²⁺ sensors present in cells, calmodulin is a highly conserved and ubiquitous Ca²⁺ sensor.³⁾

Regulation of membrane protein integration involves molecular devices such as Sec-translocons or the insertase YidC. We have identified an integration-promoting factor in the inner membrane of Escherichia coli called membrane protein integrase (MPIase). Structural analysis revealed that, despite its enzyme-like name, MPIase is a glycolipid with a long glycan comprising N-acetyl amino sugars, a pyrophosphate linker, and a diacylglycerol (DAG) anchor. Additionally, we found that DAG, a minor membrane component, blocks spontaneous integration. In this review, we demonstrate how they contribute to Sec-independent membrane protein integration in bacteria using a comprehensive approach including synthetic chemistry and biophysical analyses. DAG blocks unfavorable spontaneous integrations by suppressing mobility in the membrane core, whereas MPIase compensates for this. Moreover, MPIase plays critical roles in capturing a substrate protein to prevent its aggregation, attracting it to the membrane surface, facilitating its insertion into the membrane, and delivering it to other factors. The combination of DAG and MPIase efficiently regulates the integration of membrane proteins.

Tardigrades are microscopic animals that are renowned for their capabilities of tolerating near-complete desiccation by entering an ametabolic state called anhydrobiosis. However, many species also show high tolerance against radiation in the active state as well, suggesting cross-tolerance via the anhydrobiosis mechanism. Previous studies utilized indirect DNA damaging agents to identify core components of the cross-tolerance machinery in species with high anhydrobiosis capacities. However, it was difficult to distinguish whether transcriptomic changes were specific to DNA damage or mutual with anhydrobiosis. To this end, we performed transcriptome analysis on bleomycin-exposed Hypsibius exemplaris. We observed induction of several tardigrade-specific gene families, including a previously identified novel anti-oxidative stress family, which may be a core component of the cross-tolerance mechanism. We also identified enrichment of the tryptophan metabolism pathway, for which metabolomic analysis suggested engagement of this pathway in stress tolerance. These results provide several candidates for the core component of cross-tolerance, as well as possible anhydrobiosis machinery.