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Updated: Jan 22, 2026
Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
Enforced lysosomal biogenesis rescues erythromycin- and clindamycin-induced mitochondria-mediated cell death in human
Paresh Prajapati1,2,3, Pooja Dalwadi1, Dhruv Gohel1
1Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Sayajigunj, Vadodara, Gujarat, 390002, India.
Abstract:
Antibiotics are the front-line treatment against many bacterial infectious diseases in human. The excessive and long-term use of antibiotics in human cause several side effects. It is important to understand the underlying molecular mechanisms of action of antibiotics in the host cell to avoid the side effects due to the prevalent uses. In the current study, we investigated the crosstalk between mitochondria and lysosomes in the presence of widely used antibiotics: erythromycin (ERM) and clindamycin (CLDM), which target the 50S subunit of bacterial ribosomes. We report here that both ERM and CLDM induced caspase activation and cell death in several different human cell lines. The activity of the mitochondrial respiratory chain was compromised in the presence of ERM and CLDM leading to bioenergetic crisis and generation of reactive oxygen species. Antibiotics treatment impaired autophagy flux and lysosome numbers, resulting in decreased removal of damaged mitochondria through mitophagy, hence accumulation of defective mitochondria. We further show that over-expression of transcription factor EB (TFEB) increased the lysosome number, restored mitochondrial function and rescued ERM- and CLDM-induced cell death. These studies indicate that antibiotics alter mitochondria and lysosome interactions leading to apoptotsis and may develop a novel approach for targeting inter-organelle crosstalk to limit deleterious antibiotic-induced side effects.
Insights
Common antibiotics like erythromycin and clindamycin trigger cell death by disrupting mitochondria and lysosomes. Targeting this organelle crosstalk may reduce harmful antibiotic side effects.
Area of Science:
- Cell Biology
- Pharmacology
- Toxicology
Background:
- Antibiotics are crucial for treating bacterial infections but can cause host cell side effects.
- Understanding antibiotic mechanisms in host cells is vital to mitigate adverse effects.
- Mitochondria and lysosomes play key roles in cellular health and homeostasis.
Purpose of the Study:
- To investigate the impact of erythromycin (ERM) and clindamycin (CLDM) on mitochondria-lysosome crosstalk in human cells.
- To elucidate the molecular mechanisms underlying antibiotic-induced cell death.
- To explore potential therapeutic strategies targeting inter-organelle communication.
Main Methods:
- Exposure of human cell lines to ERM and CLDM.
- Assessment of caspase activation and cell viability.
- Analysis of mitochondrial respiratory chain activity and reactive oxygen species (ROS) generation.
- Evaluation of autophagy flux and lysosome dynamics.
- Investigation of transcription factor EB (TFEB) overexpression effects.
Main Results:
- ERM and CLDM induced caspase activation and cell death in multiple human cell lines.
- Antibiotics impaired mitochondrial function, leading to bioenergetic crisis and increased ROS.
- Autophagy flux and lysosome numbers were reduced, hindering mitophagy and causing defective mitochondria accumulation.
- TFEB overexpression restored lysosome numbers, mitochondrial function, and rescued cells from antibiotic-induced death.
Conclusions:
- Erythromycin and clindamycin disrupt mitochondria-lysosome interactions, leading to apoptosis.
- Altered inter-organelle crosstalk contributes to antibiotic-induced toxicity.
- Targeting mitochondria-lysosome communication presents a potential strategy to limit adverse antibiotic effects.
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