The therapeutic potential of mitochondrial toxins

When screening active compounds by phenotypic assays, we often encounter mitochondrial toxins, which are compounds that can affect mitochondrial functions. In normal cells, these toxins may have relatively low toxicity but can nonetheless show measurable effects even at low concentrations. On the ot...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antibiotics 2021-10, Vol.74 (10), p.696-705
Main Authors: Kawada, Manabu, Amemiya, Masahide, Yoshida, Junjiro, Ohishi, Tomokazu
Format: Article
Language:English
Subjects:
13
13/106
631/154/1435/2417
631/67/1059/153
Adenosine triphosphate
Animals
Antibiotics
Anticancer properties
Antineoplastic Agents - pharmacology
Antitumor agents
Apoptosis
Bacteriology
Biomedical and Life Sciences
Bioorganic Chemistry
Cancer
Cytochrome
Drug Delivery Systems
Drug development
Drug Discovery
Drugs
Electron transport
Enzymes
Humans
Hypoxia
Inhibitors
Life Sciences
Low concentrations
Mammals
Medicinal Chemistry
Metabolism
Metabolites
Microbiology
Microorganisms
Mitochondria
Mitochondria - drug effects
Organic Chemistry
Oxidative phosphorylation
Phosphorylation
Respiration
Special Feature: Review Article
Toxicity
Toxins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:When screening active compounds by phenotypic assays, we often encounter mitochondrial toxins, which are compounds that can affect mitochondrial functions. In normal cells, these toxins may have relatively low toxicity but can nonetheless show measurable effects even at low concentrations. On the other hand, in animals, mitochondrial toxins can exert severe toxicity. Mitochondrial toxins that act as inhibitors of respiratory chain complexes in oxidative phosphorylation (OXPHOS) are typically avoided during drug discovery efforts, as such compounds can directly promote lethal inhibition of pulmonary respiration. However, mitochondrial toxins could in fact have beneficial therapeutic effects. Anti-cancer strategies that target mitochondrial functions, particularly OXPHOS, have received increasing attention in recent years. In this review article we examine the significance of OXPHOS inhibitors as anti-cancer drug candidates and discuss compounds having microbial origins.
ISSN:0021-8820
1881-1469
DOI:10.1038/s41429-021-00436-z