The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function

Area of Science:

• Biochemistry
• Cardiology
• Cell Biology

Background:

• Mitochondria share bacterial ancestry.
• Tetracycline antibiotics inhibit bacterial protein translation.
• Doxycycline is a tetracycline antibiotic.

Purpose of the Study:

• To test if doxycycline reduces mitochondrial function.
• To investigate if doxycycline causes cardiac contractile dysfunction.
• To examine doxycycline's effects in H9C2 cardiomyoblasts, adult rat cardiomyocytes, Drosophila, and mice.

Main Methods:

• Utilized H9C2 cardiomyoblasts, adult rat cardiomyocytes, Drosophila, and mice models.
• Administered doxycycline and control antibiotics (ampicillin, carbenicillin).
• Assessed mitochondrial function (respiration, OXPHOS, complex I), protein balance, and cardiac contractility (calcium concentration, arrhythmicity, systolic/diastolic function).

Main Results:

• Doxycycline induced mitonuclear protein imbalance, reduced mitochondrial respiration, and fragmented mitochondria.
• Observed a shift from OXPHOS to glycolysis.
• Demonstrated impaired cardiac contractility, increased diastolic calcium, higher arrhythmicity, systolic/diastolic dysfunction, and exacerbated issues in a diabetes mouse model.

Conclusions:

• Doxycycline impairs mitochondrial function.
• Doxycycline causes cardiac dysfunction.
• Doxycycline's effects are linked to its inhibition of mitochondrial translation.