Key result
Lysosomal dysfunction drives cardiac fibrosis progression across multiple organelle and autophagy pathways.
Why the study?
Lysosomal dysfunction has recently been found to play a critical contributing role in modulating cardiac fibrosis through multiple mechanisms regulating lysosomal integrity, prompting a review of the molecular pathways and pharmacological targeting strategies linking lysosomal dysfunction to cardiac fibrosis progression.
This review highlights the molecular mechanisms linking lysosomal dysfunction—such as V-ATPase, TFEB, LAMP-2, and cathepsin B regulation—to the progression of cardiac fibrosis and explores potential pharmacological targets.
Answers are grounded in this paper and cite their sources.
Lysosomal targets may merit mechanistic study in fibrosis; leaves open clinical translation pending interventional trials.
Cardiac fibrosis is a critical pathological condition characterized by an excessive accumulation of extracellular matrix components resulting from persistent cellular stress, inflammation, oxidative stress, and organelle dysfunction. These insoluble fibers form a 3D matrix that is evident in numerous heart-related conditions, including myocardial infarction, heart failure, cardiomyopathies, and hypertension. Cardiomyocytes, unlike fibroblasts and endothelial cells, are post-mitotic and rely heavily on cellular quality-control systems to sustain their workload. Lysosomes, a single-lipid-bilayered membrane-bound organelle, are one of the important organelles that maintain cellular homeostasis by degrading and recycling cellular debris. Autophagy is one of the catabolic processes that is heavily reliant on lysosomes to form autolysosomes, which help degrade and recycle cellular components, proteins, and lipids, and maintain cellular homeostasis. Recently, lysosomal dysfunction has been found to play a critical contributing role in modulating cardiac fibrosis. The involvement of lysosomal dysfunction in mediating cardiac fibrosis progression involves several intriguing mechanisms that regulate lysosomal integrity, including V-ATPase, transcription factor EB (TFEB), lysosomal-associated membrane protein-2 (LAMP-2), cathepsin B, and chaperone-mediated autophagy, among others. The subsequent review, therefore, demonstrates the role of lysosomes in physiological and pathological heart conditions, with a particular emphasis on cardiac fibrosis, the central mechanism underlying the most aggressive stages of cardiac disease. The correlation between lysosomal dysfunction and cardiac fibrosis, as well as the interconnections and cellular pathways linking them, is discussed, along with emerging preclinical and clinical investigations that could be pursued to elucidate the role of lysosomal dysfunction in cardiac fibrosis progression.
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Ghosh et al. (2026) conducted a review in Cardiac fibrosis. Lysosomal dysfunction and pharmacological targeting strategies was evaluated on Cardiac fibrosis progression. Lysosomal dysfunction modulates cardiac fibrosis progression via V-ATPase, TFEB, LAMP-2, cathepsin B, and chaperone-mediated autophagy pathways.
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