Drp1-Dependent Mitochondrial Fission Contributes to Lactic Acid-Induced Chicken Cardiomyocyte Damage

Area of Science:

• Animal Science
• Cardiovascular Research
• Cell Biology

Background:

• Sudden death syndrome (SDS) in broilers is linked to enhanced glycolysis and lactic acid (LA) production.
• The precise mechanism of LA-induced cardiomyocyte damage and heart failure in fast-growing broilers requires further elucidation.

Purpose of the Study:

• To investigate the effects of LA on chicken embryo cardiomyocytes (CECs) and elucidate the underlying mechanisms of LA-induced injury.
• To explore potential therapeutic strategies for preventing LA-induced SDS in broilers.

Main Methods:

• Primary culture of chicken embryo cardiomyocytes (CECs) and treatment with lactic acid (LA).
• Assessment of CEC proliferation, contraction, apoptosis, and mitochondrial function (ultrastructure, membrane potential, dynamics).
• Evaluation of the protective effects of Mdivi-1, a Drp1 inhibitor, on LA-treated CECs.

Main Results:

• LA inhibited CEC proliferation and contraction, induced apoptosis, and disrupted mitochondrial ultrastructure and membrane potential.
• LA activated mitophagy and disturbed mitochondrial dynamics, leading to increased mitochondrial fission.
• Mdivi-1 treatment improved CEC viability, restored mitochondrial integrity, reduced reactive oxygen species, and inhibited LA-induced apoptosis.

Conclusions:

• LA-induced cardiomyocyte injury in broiler SDS is associated with mitochondrial damage and excessive mitochondrial fission.
• Inhibiting mitochondrial hyperfission with Mdivi-1 effectively preserves CEC morphology, structure, and function, crucial for preventing LA-induced damage.
• This study provides a mechanistic basis for developing strategies to prevent and control SDS in broilers.