2008 · Benchimol — The hydrogenosome as a drug target.
Super-Abstract
This in-vitro review/study describes hydrogenosomes — organelles found in certain parasitic microorganisms (such as Trichomonas) that produce molecular hydrogen — as potential drug targets for anti-parasitic therapies. Because hydrogenosome metabolism differs fundamentally from human mitochondria, drugs targeting them could selectively kill parasites without harming the host. (Current Pharmaceutical Design, 2008.)
Commentary
Hydrogenosomes are ancient, mitochondria-related organelles found in anaerobic microorganisms, including the human pathogen Trichomonas vaginalis (the cause of the most common non-viral sexually transmitted infection). The relevance to H₂ in this paper is metabolic: hydrogenosomes are named for their role in producing H₂ as a metabolic byproduct of pyruvate oxidation. This is fundamentally different from the therapeutic use of dissolved molecular H₂ as an antioxidant. This paper investigates drug targets in parasitic organisms, not the therapeutic application of H₂ in humans. The metronidazole-resistant Trichomonas problem it addresses is a real clinical challenge, and the drug-target biology is solid, but this study is irrelevant to the H₂ therapy field as typically discussed.
Key quotes
- „Hydrogenosomes are considered an excellent drug target since their metabolic pathway is distinct from those found in mitochondria and thus medicines directed to these organelles will probably not affect the host-cell.“ — the key rationale for targeting hydrogenosomes: parasite-selective toxicity
- „they are the site of molecular hydrogen formation“ — why these organelles are relevant to H₂ — they produce H₂ as a metabolic byproduct (not therapeutic)
- „The main drug used against trichomonads is metronidazole, although other drugs such as beta-Lapachone, colchicine, Taxol, nocodazole, griseofulvin, cytochalasins, hydroxyurea, among others, have been used in trichomonad studies.“ — overview of current and candidate anti-trichomonad drugs
Our assessment
This paper is not relevant to therapeutic H₂ use in humans. The H₂ connection is purely metabolic — hydrogenosomes produce H₂ as a byproduct of anaerobic energy metabolism. This is a different biological context entirely from therapeutic molecular H₂ as an antioxidant. The study is solid parasitology/drug target research. It should not be cited as evidence for H₂ health effects.
Study design
- Type: in-vitro review/mechanistic study · Model: Trichomonas vaginalis hydrogenosomes; various anti-trichomonad drug effects on organelle morphology · H₂ connection: metabolic only — hydrogenosomes produce H₂ as a byproduct; not therapeutic H₂
- Result: hydrogenosomes characterized as drug targets due to distinct metabolism; metronidazole and other drugs cause morphological disruption; hydrogenosomal H₂ production is a biochemical function, not a therapeutic tool
Abstract
Hydrogenosomes are spherical or slightly elongated organelles found in non-mitochondrial organisms. In Trichomonas hydrogenosomes measure between 200 to 500 nm, but under drug treatment they can reach 2 microm. Like mitochondria hydrogenosomes: (1) are surrounded by two closely apposed membranes and present a granular matrix: (2) divide in three different ways: segmentation, partition and the heart form; (3) they may divide at any phase of the cell cycle; (4) produce ATP; (5) participate in the metabolism of pyruvate formed during glycolysis; (6) are the site of molecular hydrogen formation; (7) present a relationship with the endoplasmic reticulum; (8) incorporate calcium; (9) import proteins post-translationally; (10) present cardiolipin. However, there are differences, such as: (1) absence of genetic material, at least in trichomonas; (2) lack a respiratory chain and cytochromes; (3) absence of the F(0)-F(1) ATPase; (4) absence of the tricarboxylic acid cycle; (5) lack of oxidative phosphorylation; (6) presence of peripheral vesicles. Hydrogenosomes are considered an excellent drug target since their metabolic pathway is distinct from those found in mitochondria and thus medicines directed to these organelles will probably not affect the host-cell. The main drug used against trichomonads is metronidazole, although other drugs such as beta-Lapachone, colchicine, Taxol, nocodazole, griseofulvin, cytochalasins, hydroxyurea, among others, have been used in trichomonad studies, showing: (1) flagella internalization forming pseudocyst; (2) dysfunctional hydrogenosomes; (3) hydrogenosomes with abnormal sizes and shapes and with an electron dense deposit called nucleoid; (4) intense autophagy in which hydrogenosomes are removed and further digested in lysosomes.
Source & links
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