Silver nanoparticles affect bidirectional crosstalk between mitochondria and lysosomes in hemocyte subtypes of the oyster Crassostrea hongkongensis

Abstract

Hemocytes are the main immune cells for defense against exogenous particles and consist of three cellular subtypes (agranulocytes, semigranulocytes, and granulocytes) with heterogeneous functions in the oyster Crassostrea hongkongensis. Mitochondria and lysosomes are recognized as the major intracellular targets of silver nanoparticles (AgNPs), but the interaction between them has been overlooked. In this study, mitochondrial fragmentation induced by AgNPs and their ionic counterparts with equivalent intracellular Ag⁺ contents was analyzed by determining mitochondrial shape, size, and network connectivity, which resulted from an increased rate of mitochondrial fission. In addition, both types of Ag species increased lysosome number and size and resulted in lysosomal and mitochondrial dysfunction, including increased lysosomal membrane permeabilization and reduced mitochondrial membrane potential. AgNPs and Ag ions could affect mitochondria–lysosome interactions, including mitochondria–lysosome contacts (MLCs) and mitophagy. Specifically, AgNPs and Ag ions prolonged the MLCs and then led to the impairment of mitochondrial structure and function. The disrupted contact untethering machinery may be due to the reduced lysosomal enzymatic activity present in the enlarged lysosomes. Furthermore, mitophagy was enhanced by AgNPs and Ag ions. Our study demonstrated that Ag ions mainly contributed to AgNP toxicity, and MLCs exerted critical roles as upstream mediators of mitochondrial dynamics and functions, which can cast light on the mechanisms of immune cell cytotoxicity of animals caused by AgNPs.