- Gentamicin, like other aminoglycoside antibiotics, primarily targets bacterial ribosomes, binding to the 30S subunit to disrupt protein synthesis and cause cell death. This mechanism is highly effective against many Gram-negative and some Gram-positive bacteria, making gentamicin a valuable tool for preventing contamination in cell culture. However, because mitochondria evolved from ancestral prokaryotes and retain 70S-type ribosomes—similar to those found in bacteria—gentamicin has the potential to affect mitochondrial function under certain conditions.
- Mitochondrial sensitivity to gentamicin arises from this structural similarity. Gentamicin may bind to mitochondrial ribosomes and interfere with the synthesis of key mitochondrial proteins. These proteins are essential for the assembly and function of respiratory chain complexes that drive oxidative phosphorylation and ATP production. Inhibition of mitochondrial translation can lead to impaired energy metabolism, generation of reactive oxygen species (ROS), and induction of apoptosis in sensitive cell types. This is particularly relevant in cells that are highly dependent on mitochondrial respiration or that are exposed to gentamicin over extended periods.
- Under standard cell culture conditions, gentamicin is typically used at concentrations between 10–50 µg/mL, which are generally well tolerated by most mammalian cell lines. Under these conditions, the effect on mitochondria is usually negligible or subclinical. However, certain primary cells, stem cells, or energy-demanding tissues may exhibit greater sensitivity, and in such cases, mitochondrial stress or dysfunction may occur even at standard doses. Additionally, cumulative effects may become apparent with long-term exposure, particularly in experiments involving mitochondrial metabolism, oxidative stress, or drug screening.
