Ageing, Neurodegeneration and Alzheimer's Disease
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
Mitochondria are critical in the production of ATP as they are the site for oxidative phosphorylation. The oxidation of NADH and FADH2, formed in glycolysis, fatty acid oxidation and the tricarboxylic acid cycle (TCA), is used to reduce ground state molecular dioxygen to water in the electron transport chain (ETC) which traverses the inner mitochondrial membrane (Zhao et al., 2019). During this process, protons are pumped into the intramembrane space to create a pH gradient and mitochondrial membrane potential (Belenguer et al., 2019), termed the proton-motive force (Mitchell, 1966). The entry of protons back into the matrix via the ATPase enzyme enables the phosphorylation of ADP to synthesis ATP (Belenguer et al., 2019). Mitochondrial oxidative phosphorylation accounts for a large portion of ATP synthesis in the brain, and therefore, a sufficient supply of metabolites is critical for effective cellular respiration. Although predominantly associated with their role in generating ATP, mitochondria are also involved in a number of other critical cellular processes, which include programmed cell death, calcium signalling, fatty acid oxidation and the innate immune response (Scott and Youle, 2010). Therefore, the development of mitochondrial dysfunction in an ageing brain would pose a significant challenge to cell function.
Introduction to lactic acidemias
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Energy conversion takes place in mitochondria in which the exergonic oxidation/reduction reactions of the electron transport chain, as in chloroplasts and bacteria, are coupled to the endergonic synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate [14]. The electron flow generates a proton motive force. The ATP synthase is a large asymmetric enzyme complex of an F0F1 structure, in which the F0 is a hydrophobic, membrane-embedded unit that serves as a proton channel, while the F1 contains the nucleotide binding sites and catalytic sites for ATP synthesis. When solubilized and uncoupled from its F0 energy source, the F1 is capable of ATP hydrolysis, and this is why it is referred to as an ATPase.
Spices as Eco-friendly Microbicides: From Kitchen to Clinic
Mahendra Rai, Chistiane M. Feitosa in Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
The mechanisms of action of the essential oils (Nazzaro et al. 2013) include: Cell wall degradation.Cytoplasmic membrane damage.Cytoplasm coagulation.Membrane proteins damage.Leakage of the cell contents.Proton motive force reduction.Intracellular ATP pool reduction via decreased ATP synthesis and augmented hydrolysis andMembrane potential reduction via increased membrane permeability.
Evaluation of the antimicrobial mechanism of biogenic selenium nanoparticles against Pseudomonas fluorescens
Published in Biofouling, 2023
Ying Xu, Ting Zhang, Jiarui Che, Jiajia Yi, Lina Wei, Hongliang Li
ATP is an important energy molecule for all living organisms and it plays a vital role in a variety of physiological processes such as respiration, metabolism, and enzymatic reactions (Li et al. 2016). Under normal circumstances, intracellular ATP levels remain in a stable state. However, the disruption of cell homeostasis and integrity may cause changes in intracellular ATP concentrations. Compared with the control group, it was found that the intracellular ATP concentrations decreased significantly after treatment with SeNPs (p < 0.05), and the extracellular ATP concentrations showed an increasing trend, among which 2 × MIC of SeNPs led to the greatest depletion (Figure 6). This depletion of cellular ATP indicated an impaired energy metabolic pathway, which in turn might impede ATP synthesis. On the other hand, SeNPs increased the cell membrane permeability, resulting in leakage of intracellular protons, so that the inside and outside of the cell membrane formed a proton gradient difference. According to the chemiosmosis theory, this gradient difference is the electromotive potential of the proton. The leakage of the proton hindered the synthesis of ATP, leading to the reduction of the intracellular ATP content (Jung et al. 2015).
Design of α-helical antimicrobial peptides with a high selectivity index
Published in Expert Opinion on Drug Discovery, 2019
Davor Juretić, Juraj Simunić
In this review, we shall mostly consider cationic linear AMPs with high selectivity and activity having at least one known or predicted amphipathic helical segment. Some natural lytic proteins, longer peptides, and bacteriocins are known to be top achievers with respect to their antibacterial activity and selectivity, but our favorites in this review will be peptides with less than 50 amino acid residues and proteinogenic amino acid residues. The focus will be on simple methods with which nature’s design can be improved by using expert knowledge, computer-guided design, and user-friendly web servers. Magainin-2 and its pexiganan (MSI-78) analogue [2] have been abundantly examined during the past 30 years [3]. They are convenient yardsticks for judging design success for other helical AMPs, either by natural evolution or by rational design. Most short AMPs, like magainins, have a random structure in an aqueous solution but are induced by bacterial-like anionic membranes to assume partially helical amphipathic conformation suitable for dynamic membrane pore formation. Subsequent short-circuits of proton transport cannot be tolerated by bacteria, which is highly dependent on creating and maintaining proton-motive force through a proton gradient and a very strong electric field. Intracellular targets for some cationic AMPs with antibiotic activity also require membrane-active peptides with the ability to interact with and pass through the cytoplasmic membrane.
Toxicity of new synthetic amphetamine drug mephedrone On Rat Heart mitochondria: a warning for its abuse
Published in Xenobiotica, 2018
Parvaneh Naserzadeh, Farzaneh Jokar, Farzaneh Vafaei, Enayatollah Seydi, Jalal Pourahmad
On one hand, our data also showed significant increased MMP collapse as an indicator of MPT pore opening after incubation of rat heart mitochondria with different concentrations of mephedrone. Furthermore, oxidation of thiol groups in the inner mitochondrial membrane could promote the MPT induction and release of cytochrome c from mitochondria as an endpoint of signaling the cell death (Bonora & Pinton, 2014; Elmore, 2007). Our results also confirmed the release of cytochrome c from mitochondria, which is related to the opening of large MPT pores in the outer membrane or inhibiting some segments of the respiratory chain in the inner membrane. The release of cytochrome c as an important part of the electron transfer between complexes III and IV will impairs mitochondrial respiratory chain activity, resulting in-uncoupling of oxidative phosphorylation (Pourahmad & Hosseini, 2012). Previous studies suggested that the Krebs cycle and electron flow in the mitochondrial respiratory chain provide the proton motive force for the transformation of ADP to ATP in the F0-F1 ATP synthesis complex (Feniouk & Junge, 2005; Fernie et al., 2004).
Related Knowledge Centers
- Cellular Respiration
- Diffusion
- Electrochemical Gradient
- Nuclear Envelope
- Osmosis
- Photosynthesis
- Semipermeable Membrane
- Ion
- Adenosine Triphosphate
- Hydrogen