Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review).

Cardiomyopathy is a complex heart disease with structural and functional defects of the myocardium, often leading to poor clinical outcomes. While traditional research has focused on myofibrillar pathology and ion channel dysfunction, emerging evidence indicates that organelle homeostasis serves a central role in the pathogenesis of the disease. Mitochondrial dysfunction disrupts energy metabolism, calcium handling, dynamics and mitophagy. Golgi fragmentation, impaired glycosylation and abnormal vesicular trafficking jeopardize protein maturation and secretion. Endoplasmic reticulum stress causes myocardial injury via unfolded protein response, calcium dyshomeostasis and disruptions of lipid metabolism. Lysosomal degradation is disrupted by autophagic dysfunction, enzyme dysregulation and calcium signaling abnormalities. Ribosomes regulate proteostasis by defective biogenesis, quality control and translational dysregulation. Nuclear envelope instability and intercalated disc dysfunction disrupt normal mechanical and gene regulation in the development of cardiomyopathy. In combination, these findings support the concept of cardiomyopathy as a multi-organelle network disease driven by coordinated dysfunction of interconnected organelles. This review systematically summarizes current evidence on organelle-specific and inter-organelle mechanisms underlying cardiomyopathy, highlighting how disrupted organelle homeostasis collectively contributes to disease initiation and progression.