Mitophagy and its regulatory mechanisms in the biological effects of nanomaterials

JOURNAL OF APPLIED TOXICOLOGY(2024)

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摘要
Mitophagy is a selective cellular process critical for the removal of damaged mitochondria. It is essential in regulating mitochondrial number, ensuring mitochondrial functionality, and maintaining cellular equilibrium, ultimately influencing cell destiny. Numerous pathologies, such as neurodegenerative diseases, cardiovascular disorders, cancers, and various other conditions, are associated with mitochondrial dysfunctions. Thus, a detailed exploration of the regulatory mechanisms of mitophagy is pivotal for enhancing our understanding and for the discovery of novel preventive and therapeutic options for these diseases. Nanomaterials have become integral in biomedicine and various other sectors, offering advanced solutions for medical uses including biological imaging, drug delivery, and disease diagnostics and therapy. Mitophagy is vital in managing the cellular effects elicited by nanomaterials. This review provides a comprehensive analysis of the molecular mechanisms underpinning mitophagy, underscoring its significant influence on the biological responses of cells to nanomaterials. Nanoparticles can initiate mitophagy via various pathways, among which the PINK1-Parkin pathway is critical for cellular defense against nanomaterial-induced damage by promoting mitophagy. The role of mitophagy in biological effects was induced by nanomaterials, which are associated with alterations in Ca2+ levels, the production of reactive oxygen species, endoplasmic reticulum stress, and lysosomal damage. Mitophagy, a form of selective autophagy that maintains mitochondrial homeostasis and protects cells, is closely associated with the pathogenesis of numerous diseases. Given the widespread use and increasing exposure of nanomaterials to the human body, it is crucial to comprehend their biological effects. Therefore, we conducted a comprehensive review of the regulatory mechanisms of mitophagy and its impact on cellular responses to nanomaterials, in order to provide intervention strategies for diagnosing and treating mitochondria-related disorders.
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关键词
cellular responses,mitophagy,nanomaterials,PINK1-Parkin pathway,regulatory mechanisms
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