A review of peroxisome biology: Potential implications for cardiac physiology and pathology

The human heart has often been described as the "metronome of life" beating continuously over 2.5 billion times across the average lifespan and consuming more than 6 kg of ATP daily. And, during both a healthy and diseased state, the heart predominately relies on the oxidation of fatty acids to fuel its contractile burden of supporting all other organ systems. While metabolic alterations and substrate utilization inflexibility have been well studied and are considered hallmarks of heart failure pathogenesis, the overwhelming majority of these investigations have focused on the health and function of the mitochondria in cardiac myocytes; for good reason given the mitochondria is the location of oxidative phosphorylation complexes that, although debated, can form respiratory super complexes to generate ATP in conjunction with the electron transport chain and TCA cycle. However, there exists a potentially overlooked supporting organelle crucial for fatty acid oxidation - the peroxisome. In addition to serving as the site of long chain fatty acid breakdown into acyl-CoA for transport into the mitochondria, the peroxisome supports cellular viability and function via several critical mechanisms (e.g. plasmalogen synthesis and reactive oxygen species quenching). Despite this, only recently have published reports started to appreciate the potential significance of peroxisomes in cardiovascular physiology. In this review, we aim to provide a global perspective on peroxisomes to include their lifecycle and function gathered mostly from seminal studies in extracardiac tissues and highlight functional roles for peroxisomes directly in the context of cardiac physiology and pathology from more recent literature.