Mitochondrial uncoupling can be defined as a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis. Although this process was originally considered a mitochondrial dysfunction, the identification of UCP-1 as an endogenous physiological uncoupling protein suggests that the process could be involved in many other biological processes. In this review, we first compare the mitochondrial uncoupling agents available in term of mechanistic and non-specific effects. Proteins regulating mitochondrial uncoupling, as well as chemical compounds with uncoupling properties are discussed. Second, we summarize the most recent findings linking mitochondrial uncoupling and other cellular or biological processes, such as bulk and specific autophagy, reactive oxygen species production, protein secretion, cell death, physical exercise, metabolic adaptations in adipose tissue, and cell signaling. Finally, we show how mitochondrial uncoupling could be used to treat several human diseases, such as obesity, cardiovascular diseases, or neurological disorders.

https://www.mdpi.com/2073-4409/8/8/795/pdf

Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases.

Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives.

Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) diblock copolymer vesicles can be prepared in the form of concentrated aqueous dispersions via polymerization-induced self-assembly (PISA). In the present study, these syntheses are conducted in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. This approach leads to encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be calculated using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. Small angle X-ray scattering (SAXS) is used to confirm silica encapsulation, since a structure factor is observed at q ≈ 0.25 nm–1. A new two-population model provid...

http://pubs.acs.org/doi/pdf/10.1021/jacs.5b10415

Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release.

Nanomaterials have revolutionized modern science and technology due to their multiple applications in engineering, physics, chemistry, and biomedicine. Nevertheless, the use and manipulation of nanoparticles (NPs) can bring serious damages to living organisms and their ecosystems. For this reason, ecotoxicity and cytotoxicity assays are of special interest in order to determine the potential harmful effects of NPs. Processes based on ecotoxicity and cytotoxicity tests can significantly consume time and financial resources. In this sense, alternative approaches such as quantitative structure–activity/toxicity relationships (QSAR/QSTR) modeling have provided important insights for the better understanding of the biological behavior of NPs that may be responsible for causing toxicity. Until now, QSAR/QSTR models have predicted ecotoxicity or cytotoxicity separately against only one organism (bioindicator species or cell line) and have not reported information regarding the quantitative influence of character...

Computational tool for risk assessment of nanomaterials: novel QSTR-perturbation model for simultaneous prediction of ecotoxicity and cytotoxicity of uncoated and coated nanoparticles under multiple experimental conditions.

Twelve gemini quaternary ammonium surfactants have been employed to evaluate the antibacterial activity and in vitro cytotoxicity. The antibacterial effects of the gemini surfactants are performed on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with minimum inhibitory concentrations (MIC) ranging from 2.8 to 167.7 μM. Scanning electron microscopy (SEM) analysis results show that these surfactants interact with the bacterial cell membrane, disrupt the integrity of the membrane, and consequently kill the bacteria. The data recorded on C6 glioma and HEK293 human kidney cell lines using an MTT assay exhibit low half inhibitory concentrations (IC50). The influences of the gemini surfactants on the cell morphology, the cell migration ability, and the cell cycle are observed through hematoxylin-eosin (HE) staining, cell wound healing assay, and flow cytometric analyses, respectively. Both the values of MIC and IC50 decrease against the growth of the alkyl chain length of the gemini surfactant...

Antibacterial Activity, in Vitro Cytotoxicity, and Cell Cycle Arrest of Gemini Quaternary Ammonium Surfactants.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide which could bind with human serum albumin (HSA) and bovine serum albumin (BSA). The binding behavior was studied employing fluorescence, three-dimensional fluorescence, Circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, electrochemistry and molecular modeling methods. The fluorescence spectra revealed that CPF causes the quenching of the fluorescence emission of serum albumin. Stern-Volmer plots were made and quenching constants were thus obtained. The results suggested the formation of the complexes of CPF with serum albumins, which were in good agreement with the results from electrochemical experiments. Association constants at 25°C were 3.039 × 10(5) mol L(-1) for HSA, and 0.3307 × 10(5) mol L(-1) for BSA, which could affect the distribution, metabolism, and excretion of pesticide. The alterations of protein secondary structure in the presence of CPF were confirmed by the evidences from UV and CD spectra. Site competitive experiments also suggested that the primary binding site for CPF on serum albumin is close to tryptophan residues 214 of HSA and 212 of BSA, which was further confirmed by molecular modeling.

Spectroscopic, structural and thermodynamic properties of chlorpyrifos bound to serum albumin: A comparative study between BSA and HSA.

Along with the widespread development of their bioapplications, concerns about the biosafety of quantum dots (QDs) have increasingly attracted intensive attention. This study examines the toxic effect and subcellular location of cadmium telluride (CdTe) QDs with different sizes against yeast Saccharomyces cerevisiae. The innovative approach is based on the combination of microcalorimetric, spectroscopic, electrochemical, and microscopic methods, which allows analysis of the toxic effect of CdTe QDs on S. cerevisiae and its mechanism. According to the values of the half inhibitory concentration (IC(50)), CdTe QDs exhibit marked cytotoxicity in yeast cells at concentrations as low as 80.81 nmol L(-1) for green-emitting CdTe QDs and 17.07 nmol L(-1) for orange-emitting CdTe QDs. QD-induced cell death is characterized by cell wall breakage and cytoplasm blebbing. These findings suggest that QDs with sizes ranging from 4.1 to 5.8 nm can be internalized into yeast cells, which then leads to QD-induced cytotoxicity. These studies provide valuable information for the design and development of aqueous QDs for biological applications.

Toxicity of CdTe Quantum Dots on Yeast Saccharomyces Cerevisiae

F16 is a novel identified delocalized lipophilic cation (DLC) which has been found to inhibiting a variety of tumor cell proliferation due to its selective accumulation in the mitochondria of carcinoma cells. To gain further insight into the thermodynamic properties of this small molecule, we chose human serum albumin (HSA) as the model protein, and investigated the interactions of F16 and its precursor compound PVI with HSA by comprehensive spectroscopy, electrochemistry and molecule modeling methods. The static fluorescence quenching of HSA suggests that both F16 and PVI can form complexes with HSA, though the binding mechanisms are different. The main driving forces for F16–HSA binding are typical hydrophobic interactions, while PVI–HSA binding takes place through electrostatic interactions. F16–HSA binding shows an adverse temperature dependence recognized as the effect of the high activation energy requirement in the binding process generated by the specific structural obstacle. Both F16 and PVI can bind with HSA and thus benefit their transportation and elimination in body, however, the positive charge of F16 may have negative effect on the binding interaction.

Investigating the interactions of a novel anticancer delocalized lipophilic cation and its precursor compound with human serum albumin

5-Fluorouracil (5-FU) was linked with F16 by vulnerable bonds to selectively target cancer mitochondria which resulted in conjugated compounds, including F16–5-FU, F16–OOC-FU, F16–NHOC-FU and F16–SS-FU. F16–OOC-FU decreased the antiproliferative activity of 5-FU on the nontumor cell line, and the cytotoxicity of F16–SS-FU significantly increased when administered with dithiothreitol (DTT).

Jia Wang

Papers

Spectroscopic, structural and thermodynamic properties of chlorpyrifos bound to serum albumin: A comparative study between BSA and HSA.

Toxicity of CdTe Quantum Dots on Yeast Saccharomyces Cerevisiae

Investigating the interactions of a novel anticancer delocalized lipophilic cation and its precursor compound with human serum albumin

Conjugated 5-fluorouracil with mitochondria-targeting lipophilic cation: design, synthesis and biological evaluation

Uncoupling Effect of F16 Is Responsible for Its Mitochondrial Toxicity and Anticancer Activity