Mitochondria, known as cellular “powerhouses,” are critical in diseases where energy production falters, such as heart failure. Current research methods often disrupt mitochondrial behavior by isolating them through techniques that damage surrounding tissue or alter their natural structure. A new PhD project aims to overcome these limitations by studying mitochondria within intact heart muscle, offering insights into their function in health and disease.
Challenges in Current Methods
Traditional mitochondrial isolation relies on mechanical disruption or ultracentrifugation, which can fragment mitochondria and distort their activity. For example, procedures involving collagenase digestion or shear stress may strip mitochondria of their protective membranes, leading to unreliable measurements of energy production. Studies show that even subtle changes in isolation methods can skew results, such as underestimating membrane potential (ΔΨ m) by failing to account for extracellular volume.
Innovative Intact-Tissue Approach
The project proposes a novel method to analyze mitochondria within intact cardiac muscle, preserving their natural environment and workload dynamics. This approach aligns with emerging techniques like nitrogen cavitation, which isolates mitochondria without ultracentrifugation, maintaining respiratory function and structural integrity. By avoiding physical disruption, researchers can observe how mitochondria adapt to varying energy demands in real time—a critical factor in heart failure progression.
Therapeutic Potential for Right-Heart Failure
The study will test whether enhancing cardiac energy efficiency improves outcomes in a right-heart failure rat model.
Previous research suggests mitochondrial dysfunction correlates with heart failure, though hyperacetylation—a common biomarker—may not directly cause respiratory deficits. By refining measurement techniques, the project could identify actionable therapeutic targets, such as stabilizing membrane potential (ΔΨ T) or optimizing mitochondrial density.
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