KU Newsletter june2021 A history of leadership

Prof. Dong-Eun Kim Identifies the Recovery Mechanism of Damaged Mitochondria

The research team of Professor Dong-Eun Kim from Department of Integrative Bioscience and Biotechnology at Konkuk Institute of Science and Technology (KIT) discovered cumulative inhibition in cells of damaged mitochondria, one of the main causes of degenerative diseases, and the mechanism of mitochondria recovery.

Under the support of Ministry of Science and ICT’s Basic Research in Science (project title: The role of keratin, fibrous protein, to maintain mitochondrial homeostasis from oxidative stress), the research was conducted by Professor Dong-Eun Kim, Dr. Areum Baek and Soo Min Sohn.

It has become highly significant to identify the mechanism of damaged mitochondria recovery and mitochondrial homeostasis as mitochondrial dysfunction turns out to be a main cause of several degenerative diseases such as Alzheimer’s disease, Parkinson’s disease and macular degeneration.

By stabilizing skeletal protein, the research team found out that damaged mitochondria by oxidative stress can be removed and the cells can be protected through maintaining homeostasis with healthy mitochondria. When a mitochondrion is damaged by oxidative stress, cell division occurs cutting off the damaged areas. The divided mitochondrion is decomposed and removed through autophagy metabolism, which involves cytoskeleton protein. The research team, however, identified that the oxidative stress changes the structure of fibrous protein, i.e. cytoskeleton protein, and the damaged mitochondria accumulated in cells in a highly inflated form result in apoptosis (image below).

Keratin 8, one of the most expressive cytoskeleton proteins in epithelial cells, mediates a plectin protein that connects intracellular fibrous structures rather than directly binds to mitochondria, where the team observed that Keratin 8 was phosphorylated and unable to be combined with mitochondria with weak interaction. The research team succeeded in maintaining mitochondrial homeostasis with by activating the division and removal of damaged mitochondria through structural stabilization of cytoskeleton proteins using medication that controls phosphorylation of Keratin 8.

The research is published online as of March 30, 2021 in Autophagy, the world’s best journal in the field of autophagocytosis. (thesis title: “KRT8 (keratin 8) attenuates necrotic cell death by facilitating mitochondrial fission-mediated mitophagy through interaction with PLEC (plectin)”)

The research result is expected to be a clue for the development of treatments for various degenerative diseases including macular degeneration by presenting a molecular mechanism that the stabilization of skeletal protein relates to mitochondrial homeostasis. The research team stated that, “Our next goal is to develop new treatments for degenerative diseases targeting action sites found in the research.” The research result was introduced as a thesis by Biological Research Information Center (BRIC) (2021.04.01.).

Professor Kim also identified a mechanism of helicase, SARS coronavirus nsP13 at the molecular level, which was recently published in Scientific Reports in March, 2020, with the recommendation ‘Faculty of 1,000’ (now renamed ‘Faculty Opinions’). (thesis title: A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicase nsP13 in the unwinding of duplex RNA)

As the most influential academic journal in life science and medical science recommending new findings and achievements, ‘Faculty of 1,000’ acknowledges the achievement of Professor Kim’s research team on developing antiviral agents of SARS-CoV-2 necessary for controlling the ongoing COVID-19 pandemic. The thesis was introduced as a recommended thesis by BRIC, as well.