Tingting Fang, Alex Chan, Janice Chew‐Harris, Toan Pham
The left ventricle (LV) is the primary pumping chamber of the heart, generating high systolic pressure to sustain systemic circulation. LV contractile dysfunction is a hallmark of various cardiovascular diseases and is associated with mitochondrial dysfunction, characterised by decreased oxidative phosphorylation (OXPHOS) capacity and increased oxidative stress. While our understanding of cardiac mitochondrial physiology has been gained from studies on LV tissues in animal models or atrial tissues in human studies, findings are often generalised across cardiac regions. Given that fundamental differences in anatomical structure, physiological function and metabolic demands exist between the LV and left atrium (LA), this study aimed to compare mitochondrial bioenergetics between LV and LA tissues from healthy rat hearts. Using high-resolution respirometry coupled with fluorimetry, we assessed mitochondrial respiration, ATP production and hydrolysis, and reactive oxygen species (ROS) production rates. Protein expression of mitochondrial respiratory complexes and antioxidant enzymes was quantified using western blotting. Our results showed that per tissue mass, LV tissues exhibited greater mitochondrial OXPHOS respiration, ATP production and hydrolysis rates, ROS production rate, and higher protein levels of mitochondrial complexes and antioxidant enzymes, consistent with higher citrate synthase activity as a marker of mitochondrial content. However, when normalised to mitochondrial content, LV tissues exhibited lower OXPHOS respiration and ATP production, expression of mitochondrial complexes and antioxidant proteins compared to LA. This study provides new insights into chamber-specific differences in mitochondrial function under physiological conditions, suggesting the importance of considering regional mitochondrial profiles in studies of cardiac mitochondrial function in health and disease.