Development of a Decision Tree for Mitochondrial Dysfunction: Uncoupling of Oxidative Phosphorylation
Steven J Enoch1, Terry W Schultz2, Ioanna G Popova3
1School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Byrom Street , L3 3AF Liverpool , England.
Chemical Research in Toxicology
|July 18, 2018
Summary
This study introduces a decision tree to categorize chemicals based on their potential for mitochondrial dysfunction, aiding in toxicological assessments. This method helps predict chronic human health and environmental risks.
Area of Science:
- Toxicology
- Computational Chemistry
- Biochemistry
Background:
- Mitochondrial dysfunction, including uncoupling of oxidative phosphorylation, is a key toxicological endpoint.
- Predictive toxicology models are crucial for assessing chemical safety.
- Understanding structure-activity relationships aids in chemical profiling.
Purpose of the Study:
- To develop a decision tree-based profiling scheme for categorizing chemicals.
- To identify structural alerts and physicochemical boundaries related to mitochondrial dysfunction.
- To integrate this scheme into the OECD QSAR Toolbox for broader application.
Main Methods:
- Literature review to identify structural alerts and physicochemical boundaries (log P, pKa).
- Development of a decision tree algorithm for chemical classification.
- Analysis of public databases within the OECD QSAR Toolbox.
- Identification of new structural alerts for protonophoric ability.
Main Results:
- A decision tree scheme was developed, assigning chemicals to six confidence-based categories.
- Physicochemical boundaries involving log P and pKa were established.
- Additional structural alerts for protonophoric concerns were identified through database analysis.
- The decision tree is set for integration into OECD QSAR Toolbox V4.3.
Conclusions:
- The developed decision tree provides a robust method for profiling chemical-induced mitochondrial dysfunction.
- This tool facilitates the grouping of chemicals for assessing chronic human health and environmental toxicological endpoints.
- The integration into the OECD QSAR Toolbox will enhance its utility in regulatory toxicology.
Related Concept Videos
01:02Phosphorylation
54.3K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
54.3K
02:40The Tree of Life - Bacteria, Archaea, Eukaryotes
38.8K
The “tree of life” describes the evolution of life and the evolutionary relationships between organisms. The root of the tree is the common ancestor to all life on Earth. All other species radiate from this point, much like the branches of a tree. The numerous tips of these branches on the tree of life represent every living, or extant, species. Extinct species, which are species that no longer exist, can be found towards the center of the tree. Currently, these organisms, both...
38.8K
02:59Animal Mitochondrial Genetics
9.3K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
9.3K
01:19Survival Tree
433
Survival trees are a non-parametric method used in survival analysis to model the relationship between a set of covariates and the time until an event of interest occurs, often referred to as the "time-to-event" or "survival time." This method is particularly useful when dealing with censored data, where the event has not occurred for some individuals by the end of the study period, or when the exact time of the event is unknown.
Building a Survival Tree
Constructing a...
Building a Survival Tree
Constructing a...
433
03:14Oxidation Numbers
42.9K
In redox reactions, the transfer of electrons occurs between reacting species. Electron transfer is described by a hypothetical number called the oxidation number (or oxidation state). It represents the effective charge of an atom or element, which is assigned using a set of rules.
42.9K
02:16Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes
16.4K
The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
16.4K