Cytochrome c (cyt c) is an electron transporter of the mitochondrial respiratory chain. Upon permeabilization of the mitochondrial outer membrane, cyt c is released into the cytoplasm, where it triggers the intrinsic pathway of apoptosis. Cytoplasmic cyt c can further reach the bloodstream. Apoptosis inhibition is one of the hallmarks of cancer and its induction in tumors is a widely used therapeutic approach. Apoptosis inhibition and induction correlate with decreased and increased serum levels of cyt c, respectively. The quantification of cyt c in the serum is useful in the monitoring of patient response to chemotherapy, with potential prognosis value. Several highly sensitive biosensors have been developed for the quantification of cyt c levels in human serum. Moreover, the delivery of exogenous cyt c to the cytoplasm of cancer cells is an effective approach for inducing their apoptosis. Similarly, several protein-based and nanoparticle-based systems have been developed for the therapeutic delivery of cyt c to cancer cells. As such, cyt c is a human protein with promising value in cancer prognosis and therapy. In addition, its thermal stability can be extended through PEGylation and ionic liquid storage. These processes could contribute to enhancing its therapeutic exploitation in clinical facilities with limited refrigeration conditions. Here, I discuss these research lines and how their timely conjunction can advance cancer therapy and prognosis.

Describing diet-related effects on the gut microbiome is essential for understanding its interactions with fat and/or sugar-rich diets to promote obesity-related metabolic diseases. Here, we sequenced the V3-V4 hypervariable region of the bacterial 16S rRNA gene to study the composition and dynamics of the gut microbiome of adult mice fed diets rich in fat and/or sugar, at 9 and 18 weeks of diet. Under high-fat, high-sugar diet, the abundances of Tuzzerella and Anaerovorax were transiently increased at 9 weeks, while Lactobacillus remained elevated at 9 and 18 weeks. The same diet decreased the abundances of Akkermansia, Paludicola, Eisenbergiella, and Butyricicoccus at 9 and 18 weeks, while Intestinimonas and UCG-009 of the Butyricicoccaceae family responded only at 18 weeks. The high-fat diet decreased the abundances of UBA1819 at 9 weeks, and Gastranaerophilales, Clostridia UCG-014, and ASF356 at 9 and 18 weeks. Those of Marvinbryantia, Harryflintia, Alistipes, Blautia, Lachnospiraceae A2, Eubacterium coprostanoligenes group, and Eubacterium brachy group were lowered only at 18 weeks. Interestingly, these genera were not sensitive to the high-sugar diet. The mouse gut microbiome was differentially affected by diets rich in fat or fat and sugar. The differences observed at 9 and 18 weeks indicate a progressive microbiome response.

Cyclic nucleotide-regulated ion channels are present in bacteria, plants, vertebrates, and humans. In higher organisms, they are closely involved in signaling networks of vision and olfaction. Binding of cAMP or cGMP favors the activation of these ion channels. Despite a wealth of structural and studies, there is a lack of structural data describing the gating process in a full-length cyclic nucleotide-regulated channel. We used high-resolution atomic force microscopy (AFM) to directly observe the conformational change of the membrane embedded bacterial cyclic nucleotide-regulated channel MlotiK1. In the nucleotide-bound conformation, the cytoplasmic cyclic nucleotide-binding (CNB) domains of MlotiK1 are disposed in a fourfold symmetric arrangement forming a pore-like vestibule. Upon nucleotide-unbinding, the four CNB domains undergo a large rearrangement, stand up by ∼1.7 nm, and adopt a structurally variable grouped conformation that closes the cytoplasmic vestibule. This fully reversible conformational change provides insight into how CNB domains rearrange when regulating the potassium channel.

Editorial: Altered Expression of Proteins in Cancer: Function and Potential Therapeutic Targets

Background: Arabidopsis thalianatransthyretin-like (TTL) protein is a potential substrate in the brassinosteroid signalling cascade, having a role that moderates plant growth. Moreover, sequence homology revealed two sequence domains similar to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) decarboxylase (N-terminal domain) and 5-hydroxyisourate (5-HIU) hydrolase (C-terminal domain). TTL is a member of the transthyretin-related protein family (TRP), which comprises a number of proteins with sequence homology to transthyretin (TTR) and the characteristic C-terminal sequence motif Tyr-Arg-Gly-Ser. TRPs are single domain proteins that form tetrameric structures with 5-HIU hydrolase activity. Experimental evidence is fundamental for knowing if TTL is a tetrameric protein, formed by the association of the 5-HIU hydrolase domains and, in this case, if the structural arrangement allows for OHCU decarboxylase activity. This work reports about the biochemical and functional characterization of TTL.Results: The TTL gene was cloned and the protein expressed and purified for biochemical and functional characterization. The results show that TTL is composed of four subunits, with a moderately elongated shape. We also found evidence for 5-HIU hydrolase and OHCU decarboxylase activitiesin vitro, in the full-length protein.Conclusions: TheArabidopsis thalianatransthyretin-like (TTL) protein is a tetrameric bifunctional enzyme, since it has 5-HIU hydrolase and OHCU decarboxylase activities, which were simultaneously observedin vitro.