The heart's high energy demands are primarily fulfilled through mitochondrial fatty acid (FA) β-oxidation, with lipid droplets (LDs) being the main source of FAs. Research indicates that cardiac lipid homeostasis relies on a dynamic interaction between LDs and mitochondria, facilitated by specialized membrane contact sites (MCSs). These sites are marked by essential proteins such as the Perilipin (PLIN) family, mitochondrial dynamics proteins, and Rab GTPases, forming an efficient pathway for transferring FAs from storage to mitochondrial oxidation. This protective mechanism helps to avert the accumulation of lipotoxic intermediates while supporting lipid synthesis during periods of nutrient surplus. Conversely, the dysregulation of this mitochondria-LD axis is often implicated in various metabolic cardiovascular diseases (CVDs), including heart failure, atherosclerosis, and diabetic cardiomyopathy. Such imbalances lead to interconnected pathological processes, including cardiomyocyte lipotoxicity and mitochondrial dysfunction, which ultimately contribute to myocardial injury and pathological cardiac growth and fibrosis. This review comprehensively examines the current understanding of this intricate organelle crosstalk, emphasizing its structural and functional aspects, diverse biological roles, and significant implications for CVD pathogenesis. A deeper insight into and targeted modulation of this axis could pave the way for innovative therapeutic strategies aimed at addressing metabolic CVDs.
Chi et al. (Tue,) studied this question.