There's a popular group of antibiotics known as fluoroquinolones, abbreviated FQs. They're quinolone abx with a fluorine atom added at position 6 to increase cell permeability. Popular varieties of these drugs include ciprofloxacin, levofloxacin, norfloxacin, and many others. They also go by brand names Cipro, Levaquin, etc. They have a well known side effect of wreaking havoc on the body's mitochondria through numerous pathways.
This stunning image shows the in-vitro result of administering a clinically relevant dose of ciprofloxacin to human tissue for 24 hours (1). The study notes "short, swollen, fragmented mitochondria (smaller aspect ratio) with highly reduced branching (smaller form factor)"
Because the fluorine atom allows for deep tissue penetration, FQs can cross the double membrane of mitochondria, and because FQs are designed to target "double helix" DNA of some bacteria, they also appear capable of targeting the same double helix DNA structure in mitochondria. In bacteria, the FQs bind to the DNA-gyrase, causing breaks in the DNA that are fatal (2) to the bacteria.
A study published in Molecular Pharmacology (3) shows that mtDNA is "depleted" by Cipro:
Analysis of mtDNA from ciprofloxacin-treated cells revealed the presence of site-specific, double-stranded DNA breaks. These results suggest that ciprofloxacin may be causing cytotoxicity by interfering with a mitochondrial topoisomerase II-like activity, resulting in a loss of mtDNA.
The full text of this study is not available as far as I can tell. I can find scientific literature on depletion of mtDNA (4) but what does this mean for the long term health of the mitochondria / cell?
- Can mitochondria with "depleted" mtDNA reproduce, passing on the damage from breaks in the DNA? Or is the mitochondria and cell doomed?
- More open ended: Is there any literature suggesting mitochondria damaged by oxidative stress can recover (first image), or are they also doomed?