Mitochondrial homeostasis collapse to cardiac remodeling: From mechanisms to novel targeted therapeutic avenues

Abstract

Myocardial remodeling is a common pathological process in various cardiovascular diseases (CVDs) and represents the heart's adaptive response to pressure or volume overload. However, prolonged myocardial remodeling often leads to a progressive decline in cardiac function, ultimately resulting in heart failure (HF). This process is primarily characterized by myocardial hypertrophy and fibrosis, both of which are closely linked to mitochondrial dysfunction. Emerging research uncovers a pivotal orchestrator of this lethal transition: mitochondrial homeostasis. As the powerhouse of cardiomyocytes, dysfunctional mitochondria ignite a catastrophic cascade-energy bankruptcy, oxidative tsunamis, and apoptotic avalanches-propelling pathological hypertrophy and fibrosis. Although extensive research has explored mitochondrial homeostasis in cardiovascular diseases, a comprehensive summary of the specific mechanisms and effects of mitochondrial dysfunction in myocardial remodeling remains lacking. This review focuses on pathological myocardial remodeling associated with mitochondrial abnormalities and examines four critical factors: mitochondrial Ca²⁺ signaling, metabolism, dynamics, and mitophagy. Bridging molecular mechanisms to next-generation therapeutics, we systematically evaluates their roles in disease progression and discusses potential mitochondrial-targeted therapeutic strategies, offering new insights into research and treatment approaches for related conditions.

Keywords: Ca(2+); Dynamics; Metabolism; Mitochondrial homeostasis; Mitophagy; Myocardial remodeling.