12 research outputs found
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Distinct Spatiotemporal Dynamics of Peptidoglycan Synthesis between Mycobacterium smegmatis and Mycobacterium tuberculosis
Peptidoglycan (PG), a polymer cross-linked by d-amino acid-containing peptides, is an essential component of the bacterial cell wall. We found that a fluorescent d-alanine analog (FDAA) incorporates chiefly at one of the two poles in Mycobacterium smegmatis but that polar dominance varies as a function of the cell cycle in Mycobacterium tuberculosis: immediately after cytokinesis, FDAAs are incorporated chiefly at one of the two poles, but just before cytokinesis, FDAAs are incorporated comparably at both. These observations suggest that mycobacterial PG-synthesizing enzymes are localized in functional compartments at the poles and septum and that the capacity for PG synthesis matures at the new pole in M. tuberculosis. Deeper knowledge of the biology of mycobacterial PG synthesis may help in discovering drugs that disable previously unappreciated steps in the process
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Therapy-related Myeloid Neoplasm: A Study from The Chronic Malignancies Working Party of the EBMT
Target-Based Screen Against a Periplasmic Serine Protease That Regulates Intrabacterial pH Homeostasis in <i>Mycobacterium tuberculosis</i>
<i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) maintains its intrabacterial pH (pH<sub>IB</sub>) near neutrality in the acidic environment of phagosomes within
activated macrophages. A previously reported genetic screen revealed
that <i>Mtb</i> loses this ability when the mycobacterial
acid resistance protease (<i>marP</i>) gene is disrupted.
In the present study, a high throughput screen (HTS) of compounds
against the protease domain of MarP identified benzoxazinones as inhibitors
of MarP. A potent benzoxazinone, BO43 (6-chloro-2-(2âČ-methylphenyl)-4H-1,3-benzoxazin-4-one),
acylated MarP and lowered <i>Mtb</i>âs pH<sub>IB</sub> and survival during incubation at pH 4.5. BO43 had similar effects
on MarP-deficient <i>Mtb</i>, suggesting the existence of
additional target(s). Reaction of an alkynyl-benzoxazinone, BO43T,
with <i>Mycobacterium bovis</i> variant <i>bacille
Calmette-GueÌrin</i> (<i>BCG</i>) followed by
click chemistry with azido-biotin identified both the MarP homologue
and the high temperature requirement A1 (HtrA1) homologue, an essential
protein. Thus, the chemical probe identified through a target-based
screen not only reacted with its intended target in the intact cells
but also implicated an additional enzyme that had eluded a genetic
screen biased against essential genes