Mitochondrial quality control and neurodegenerative diseases

      Our laboratory focuses on understanding the roles of mitochondrial quality control and metabolism in neurodegenerative diseases. We use unbiased proteomics and genomics, cellular and molecular biology, patient iPS cells-derived cell culture and diseased animals to investigate the fundamental mechanisms by which mitochondrial impairment contributes to cellular metabolism disturbance and neurodegeneration. We also utilize rationally designed peptide inhibitors of protein-protein interactions and the high throughput screening approach to developing “mitochondrial medicine” as therapeutic strategies for treating neurodegenerative diseases.

Mitochondria are critical organelles for cellular function by regulating energy metabolism, ATP generation, and calcium handling. Dysfunctional mitochondria elicit ROS production and deficits in metabolic activity, which ultimately affect numerous biological processes, including cellular bioenergetics, immune response, genomic stability, and programmed cell death. 

To attenuate negative effects, mitochondria deploy several quality control pathways essential to maintain their pleiotropic functions and reduce mitochondrial stress. Mitochondrial quality control includes mitochondrial dynamics (fusion/fission), mitochondrial unfolded protein response (UPRmt), and mitochondria-related autophagy (mitophagy). These events repair damaged mitochondrial proteins, facilitate mitochondrial adaption to the stress, and remove/degrade the irreversibly damaged mitochondria. 

One of our research focuses is to understand the roles of mitochondrial dynamics-related proteins in mitochondrial and cellular functions, especially in the context of neurodegenerative diseases. Using a set of inhibitors targeting aberrant mitochondrial fission, we determine whether manipulation of mitochondrial dynamics could provide a useful strategy for the treatment of neurodegenerative diseases. As another arc of research, we utilize unbiased proteomics to identify factors that participate in UPRmt and mitophagy regulation. We aim to understand how protein homeostasis of mitochondria controls cell life and influences neurodegeneration.