**5. Conclusions**

In summary, Cr(VI) treatment inhibited the activity of MRCC I and enhanced ROS generation in L02 hepatocytes, leading to the translocation of Drp1 from the cytoplasm to mitochondria, subsequently inducing excessive fission and fragmentation of mitochondria. The resulted imbalance of mitochondrial dynamics decreased mtDNA copy number and mitochondrial mass, and then impaired mitochondrial function, mainly manifestation as the collapse of MMP, the exhaustion of ATP, the abnormal opening of mPTP, and the mitochondrial release of apoptosis-inducing factors such as AIF and Cyt c. Eventually, Cr(VI)-cytotoxicity was characterized by the increase of ALT/AST leakage, the enhancement of caspase-3 activity, and apoptosis (Figure 8). In this process, it is not clear whether phosphorylation or other modifications of Drp 1 occurs, and this is also our next research direction.

**Figure 8.** Summary chart of the research content of this paper. Increased mitochondrial fragmentation mediated by Drp1 contributes to Cr(VI)-induced MRCC I-dependent cytotoxicity.

**Author Contributions:** Conceptualization and supervision, F.X.; methodology, software, and validation, Y.M., Y.Z. and Y.X.; formal analysis and investigation, Y.Z. and Y.X.; writing—original draft preparation, F.X. and Y.Z. All authors have read and agreed to the published version of the manuscript.

**Funding:** The current work was supported by the National Natural Science Foundation of China (NO. 81773478) and the Natural Science Foundation of Hunan Province, China (NO. 2019JJ40402).

**Acknowledgments:** We thank Caigao Zhong in this laboratory for his valuable suggestions.

**Conflicts of Interest:** The authors declare no conflict of interest.
