| Autophagy, a vital catabolic process that degrades cytoplasmic components within the lysosome, serves as an essential cytoprotective response to pathologic stresses, such as starvation, hypoxia and peroxide. It is activated under stressful situations for quality control and regulates cellular homeostasis after DNA damage and also has a pivotal role in the maintenance of nuclear and mitochondrial DNA integrity. In autophagic process, portions of the cytoplasm and organelles are fused with lysosomes then degraded within the fused visicles. The selective degradation of mitochondria by autophagy is called mitophagy and contributes to cell survival by removing damaged or unnecessary mitochondria, which is an important mehanism for mitochondrial quality control. RecQL4, a member of human DNA helicase family, is involved in multiple DNA repair pathways. Our previous findings demonstrated that RecQL4 was involved in maintenance and integrity of the mitochondrial DNA. In this work, we focus on the role of RecQL4 in autophagy and apoptosis. In RecQL4 knockout U2OS cells, the expression level of autophagy-related protein LC3 was elevated significantly. Subcellular distribution of exogenous GFP-LC3 puncta increased in RecQL4 knockdown cells. These results indicate that RecQL4 deficiency results in increased autophagy in U2OS cells. In contrast to general autophagy, the mitophagy level did not increase in RecQL4 knockout U2OS cells, and mitophagy level changed little when treated RecQL4 knockout cells with the mitochondrial toxin rotenone. RecQL4 knockout cells were more susceptible to apoptosis under mitochondrial stress. These results demonstrated that RecQL4 was essential for efficient mitophagy induction; RecQL4 knockout may suppress mitophagy to enhance apoptosis; RecQL4 might play a different role in autophagy that is not related to mitophagy. We also did similar experiments in RecQL4 knockdown cells, the results support the conclusions described above. |
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