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High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment

2018; Elsevier BV; Volume: 15; Issue: 1 Linguagem: Inglês

10.1016/j.nano.2018.09.003

1549-9642

Chengyong He, Shengwei Jiang, Huan Yao, Liyin Zhang, Chuanli Yang, Shan Jiang, Fengkai Ruan, Deng-Lin Zhan, Gang Liu, Zhongning Lin, Yu‐Chun Lin, Xiaohong Chen,

Graphene and Nanomaterials Applications

Mitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive than assays and detections for cell viability and mitochondrial functions. Of which, superparamagnetic iron oxide (SPIO)-NPs or graphene oxide-quantum dots (GO-QDs) was selected as representatives for positive or negative inducer of mitophagy. SPIO-NPs, but not GO-QDs, activated PINK1-dependent mitophagy as demonstrated by recruitment of PARKIN to mitochondria and degradation of injured mitochondria. SPIO-NPs caused the loss of mitochondrial membrane potential, decrease in ATP, and increase in mitochondrial reactive oxide species and Ca2+. Blocking mitophagy with PARKIN siRNA aggravated the cytotoxicity of SPIO-NPs. Taken together, PINK1 immunofluorescence-based HCA is considered to be an early, sensitive, and reliable approach to evaluate the bioimpacts of NPs.