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

Cells. 2019 Oct 11;8(10):1241. doi: 10.3390/cells8101241.

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: ROS; lipid droplet; mitochondria; perilipin 5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hep G2 Cells
  • Humans
  • Lipid Droplets / metabolism
  • Lipid Metabolism / physiology
  • Mitochondria / metabolism
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Perilipin-5 / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • Perilipin-5
  • Plin5 protein, mouse
  • Reactive Oxygen Species