Mitochondria are critical organelles for cellular function through regulation of metabolism, ATP generation, and calcium handling. Dysfunctional mitochondria elicit the inordinate production of ROS and the deficits in metabolic activity, which ultimately affect numerous biological processes, including cellular bioenergetics, immune response, genomic stability and programmed cell death.
To attenuate these negative effects, mitochondria deploy several quality control pathways that are 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 are to repair damaged mitochondrial proteins, to facilitate mitochondrial adaption to the stress and to remove/degrade the irreversibly damaged mitochondria.
Mitochondrial dynamics and neurodegenerative diseases
Mitochondria are highly dynamic organelles that constantly divide and fuse in cells. Mitochondrial fission and fusion (mitochondrial dynamics) influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, and cell death. Our research goal is to understand the roles of mitochondrial dynamics (fusion and fission)-related proteins in the regulation of mitochondrial function, genome stability, lipid metabolism, and neuron-glia communication, in Huntington’s, Parkinson’s and Alzheimer’s diseases.
Mitochondrial protein and organelle homeostasis under normal and diseased conditions
Mitochondrial proteostasis and mitochondria-associated autophagy (mitophagy) are events that are important to maintaining mitochondrial proteins and organelle quality. Using an unbiased proteomics approach, we are identifying factors that participate in these events, and aim to understand how protein homeostasis of mitochondria controls neuronal life, mediates cellular communications, and influences neurodegeneration.
Development of mitochondrial enhancers for treatment of human diseases
As another arc of our research, we have been developing therapeutic options for the treatment of neurological disorders by targeting damaged mitochondria. We utilize rationally designed peptide inhibitors of protein-protein interactions and high throughput screening to developing “mitochondrial medicine” as therapeutic strategies for treating neurodegenerative diseases and other diseases in which mitochondrial dysfunction manifests.