Mitochondrial ATP synthase is vital not only for cellular energy production but also for energy dissipation and cell death. ATP synthase c-ring was suggested to house the leak channel of mitochondrial permeability transition (mPT), which activates during excitotoxic ischemic insult. In this present study, we purified human c-ring from both eukaryotic and prokaryotic hosts to biophysically characterize its channel activity. We show that purified c-ring forms a large multi-conductance, voltage-gated ion channel that is inhibited by the addition of ATP synthase F1 subcomplex. In contrast, dissociation of F1 from FO occurs during excitotoxic neuronal death suggesting that the F1 constitutes the gate of the channel. mPT is known to dissipate the osmotic gradient across the inner membrane during cell death. We show that ATP synthase c-subunit knock down (KD) prevents the osmotic change in response to high calcium and eliminates large conductance, Ca2+ and CsA sensitive channel activity of mPT. These findings elucidate the gating mechanism of the ATP synthase c-subunit leak channel (ACLC) and suggest how ACLC opening is regulated by cell stress in a CypD-dependent manner.

Probiotics have been widely explored in production, research, environmental protection, and disease prevention. Recent efforts have been devoted to the separation of new probiotics from microbes that have never been discovered and the research of their mechanism of action. PBDB, it is a database that collects probiotics from different fermented foods. It has been established and collected 1730 known probiotics (768 production, 264 research, 22 environmental protection, 17 disease control, 659 others) providing the biological information for use in humans, animals, and plants. The database will be updated and expanded periodically. The database can provide empirical data for better comprehension and application in bioinformatic studies. The potential function of the database has been confirmed by the included database, which allows for the analysis of biological information and the mechanisms of probiotics to predict new probiotics from unknown microbial resources. PBDB can be accessed at http://www.lzubiodrugs.com/.

Gastrodiae Rhizoma and its active constituents are known to exhibit neuroprotective effects in Alzheimer’s disease (AD). However, the effect of Rhizoma Gastrodiae water extract (WERG) on AD and the detailed mechanism of action remain unclear. In this study, the mechanism of action of WERG was investigated by the microbiome–gut–brain axis using a D-galactose (D-gal)/AlCl3-induced AD mouse model. WERG improved the cognitive impairment of D-gal/AlCl3-induced mice. The expression level of p-Tauthr231 in the WERG-H treatment group was decreased, and p-Tauthr231 was found negative in hippocampal DG, CA1, and CA3 regions. Here, the diversity and composition of the gut microbiota were analyzed by 16sRNA sequencing. WERG-H treatment had a positive correlation with Firmicutes, Bacilli, Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri. Interestingly, the Rikenellaceae-RC9 gut group in the gut increased in D-gal/AlCl3-induced mice, but the increased L. johnsonii, L. murinus, and L. reuteri reversed this process. This may be a potential mechanistic link between gut microbiota dysbiosis and P-TauThr231 levels in AD progression. In conclusion, this study demonstrated that WERG improved the cognitive impairment of the AD mouse model by enriching gut probiotics and reducing P-TauThr231 levels.

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