Written by: Sayan Roychowdhury
Written by: Sravya Kotaru
Original article: Liu et al. BioMed Research International 2020
The Gist of It:
Paraquat is a common herbicide used to kill weeds in croplands. It is poisonous if consumed, breathed, or touched. Severe poisoning can cause multiple organ failure including lungs, kidneys, and liver, and can be fatal. Even mild poisoning leads to long-term respiratory issues from lung damage and scarring. The usage of paraquat is highly debated; it is banned in Europe but is still widely used in the United States and other parts of the world. The people at most risk of exposure are those using the herbicide and those living in areas near where it is used, but it is also possible for paraquat to contaminate food and water sources and reach consumers. Once paraquat enters the human body, it produces harmful molecules called reactive oxygen species (ROS), which cause inflammation and tissue damage. Specifically, in the lungs, paraquat damages the tiny air sacs called alveoli, which are like small balloons that fill with air during each breath. In the alveoli, oxygen from the air diffuses into the bloodstream. When paraquat is breathed in and reaches these lung alveoli, it causes inflammation and the build-up of scar tissue around these air sacs. This scarring restricts the alveoli’s ability to expand with each breath, causing shortness of breath and lung disease. So far, there is no antidote or treatment for paraquat poisoning. Excitingly, scientists at North Sichuan Medical College in China recently discovered more details about how paraquat causes lung damage, allowing them to identify a potential target for treatment. They found that the ROS produced by paraquat lung poisoning in rats damaged mitochondria, the energy factories in alveolar air sacs. This damage turns on two proteins called PINK1 and Parkin that are responsible for removal of the damaged mitochondria and cause scar tissue to develop around damaged alveoli, thus causing lung injury. The researchers also found that deleting the protein PINK1 from lung cells grown in the laboratory prevented the production of fibronectin and collagen, two molecules that form scar tissue. These results are good news because they suggest that PINK1 could be targeted to develop a paraquat antidote and prevent lung damage. This possibility must be further explored.
The Nitty Gritty:
Paraquat, a common herbicide, is a known oxidant that generates ROS and causes mitochondrial damage in alveolar epithelial cells, resulting in alveolitis and pulmonary fibrosis. Independently, it is known that damaged mitochondria accumulate the kinase PINK1 on their outer membrane; PINK1 in turn recruits Parkin to initiate mitophagy. The authors investigated whether PINK1-Parkin signaling and mitophagy are involved in paraquat-mediated poisoning. They observed that in rat models, paraquat exposure resulted in loss of alveolar architecture and a build-up of fibrous extracellular matrix in lungs over time, indicative of fibrosing alveolitis. The poisoned rat lungs also showed a time-dependent increase in the expression of the extracellular matrix fibers fibronectin (FN) and collagen (COL-1), which contribute to the formation of fibrous scar tissue. In addition, there was a time-dependent increase in PINK1 and Parkin expression and loss of mitochondrial membrane potential, indicative of mitophagy. The researchers observed similar results in the cultured A549 lung cancer cell line, where paraquat induced a time- and dose-dependent loss in cell viability and increase in the expression of PINK1, Parkin, FN, and COL-1. Moreover, silencing PINK1 expression in A549 cells negated the effects of paraquat-mediated upregulation of Parkin, FN, and COL-1 expression. Thus, mitophagy and fibrosis due to paraquat poisoning appear to be PINK1-dependent, and PINK1 is a possible molecular target for the development of a paraquat-specific antidote.
Original Research Article: Liu, K., et al. “Paraquat exposure induces pulmonary cell mitophagy by enhancing the PINK1/Parkin signaling.” BioMed Res Int 6 (2020): 1–6. doi: 10.1155/2020/7103105.
Written by: Abby Stahl