*Article* **Perilipin 5 Protects against Cellular Oxidative Stress by Enhancing Mitochondrial Function in HepG2 Cells**

#### **Yanjie Tan 1,**†**, Yi Jin 1,**†**, Qian Wang 1, Jin Huang 1, Xiang Wu 1 and Zhuqing Ren 1,2,\***


Received: 12 July 2019; Accepted: 8 October 2019; Published: 11 October 2019

**Abstract:** Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that *Perilipin 5* (*PLIN5*), a key LD protein related to mitochondria–LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of *PLIN5* were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (*p* < 0.05). Additionally, the overexpression of *PLIN5* promoted LD formation and mitochondria–LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as *COX* and *CS*. Knockdown *PLIN5*, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated *PLIN5* expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of *PLIN5* is a kind of survival strategy for cells in response to stress. *PLIN5* can be a potential therapeutic target in NAFLD.

**Keywords:** perilipin 5; lipid droplet; mitochondria; ROS
