The nucleolus is recognized as the largest and most architecturally complex membrane-less organelle within the mammalian nucleus, exhibiting pronounced structural dynamics. Notably, this compartment demonstrates exceptional sensitivity to cellular stress; such perturbations frequently culminate in nucleolar stress, a condition characterized by structural disintegration, functional compromise, and organellar destabilization. Nucleolar stress has emerged as a critical paradigm, positing the nucleolus as both a stress sensor and a signaling hub under pathological conditions. Mechanistically, nucleolar stress responses have been demonstrated to exert pleiotropic regulatory effects on cell cycle progression, differentiation and cell fate determination, thereby triggering apoptosis, senescence, or autophagy in stressed cells. The nucleolus, being the principal site of ribosomal biogenesis and cell cycle control, has been implicated in the pathogenesis of cardiovascular disorders. Clinical and experimental evidence consistently reveals distinct nucleolar morphological aberrations and ribosomal dysfunction during cardiovascular stress events, particularly in myocardial infarction and cardiomyopathy. These disruptions have been shown to impair cardiac proteostasis and metabolic homeostasis, consequently exacerbating myocardial dysfunction. Therefore, elucidating the molecular mechanisms underlying stress-induced nucleolar signaling pathways may provide two key translational benefits: the identification of novel diagnostic biomarkers for early cardiovascular disease detection, and the discovery of precision therapeutic targets. Such advancements could substantially refine clinical management strategies and improve patients’ prognoses.
Xu et al. (2026) studied this question.