A project on which Xin Jie Chen, PhD, has been working for a decade provides insight into the physiological impact of mitochondrial dysfunction, which is associated with an increasing number of aging-related neuromuscular degenerative diseases.

Chen is a professor of biochemistry and molecular biology at Upstate and principal investigator of the study that was published in the July 20 online edition of the journal Nature. The lead author of the paper is research scientist Xiaowen Wang.

The research team identified a new pathway that can kill cells by attacking the mitochondria, a key part of the cell that produces energy. Calling it mPOS for mitochondrial precursor over-accumulation stress, this new pathway is triggered by conditions that interfere with the integrity and function of the mitochondrial inner membrane. As a result, proteins that are normally transported into mitochondria get stuck outside of the organelle, and they become toxic to the cell. Conditions that promote mPOS may contribute to the development of several muscle and cardiac diseases and neurodegenerative disorders.

“The more research that allows us to gain greater knowledge of how mitochondrial dysfunction induces cell deterioration during aging, the better our chances of developing drugs that delay the onset of cell death and may hold greater hope for drug therapies against these neuromuscular degenerative diseases,” Chen said.

In addition to discovering the new pathway, the team also identified a network of anti-degenerative genes in yeast that can protect against the mPOS, by detoxifying the dislocated mitochondrial proteins and thereby readjusting cell activity. The anti-degenerative genes are highly conserved in humans, and are mutated in several neuromuscular diseases, including myotonic dystrophy and spinocerebellar ataxia. The discovery also has implications for amyotrophic lateral sclerosis, or Lou Gehrig‘s disease.

“Dr. Chen‘s results provide novel insights into the cellular consequences of mitochondrial damage that could ultimately suggest new treatments for diseases associated with mitochondrial dysfunction,” said Patricia Kane, PhD, professor and chair of the department of biochemistry and molecular biology.



This article appears in the fall 2015 issue of Upstate Health magazine.