Mitochondria are critical organelles for cellular function through regulation of energy metabolism, ATP generation, and calcium handling. Dysfunctional mitochondria elicit the inordinate production of ROS and the deficits in energy supply, 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 (mtUPR) 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.
Understanding the role of mitochondrial dynamics in 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. One of our research interests is to understand the roles of mitochondrial dynamics (fusion and fission)-related proteins in regulation of mitochondrial and cellular functions, especially in Huntington’s, Parkinson’s and Alzheimer’s diseases. Using a set of inhibitors targeting aberrant mitochondrial fission, we are determining whether manipulation of mitochondrial dynamics could provide useful therapeutics for the treatment of neurodegenerative diseases.
Elucidating mechanisms of mitochondrial protein homeostasis and mitophagy under normal and diseased conditions
Mitochondrial proteostasis and mitochondria-associated autophagy (mitophagy) are events that are important to maintain mitochondrial proteins and organelle quality. Using unbiased proteomics approach, we are identifying factors which participate in these events, and aim to understand how protein homeostasis of mitochondria controls neuronal life and influences neurodegeneration