PI: Pin-Chao Liao, Ph.D.
Research
The mechanism of the mitochondria-associated degradation (MAD) pathway
MAD, one of the mitochondrial quality control pathways, has been shown involved in turnover of mitochondrial outer membrane proteins. We identify several MAD substrates not only on mitochondrial outer membrane but also within mitochondria using yeast as a model system. We will further elucidate the detailed mechanism of MAD pathway, explore this pathway in Drosophila, and the role of MAD in healthspan.
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(Left) Mitochondrial redox state. Warmer and cooler colors represent more reducing and oxidizing environments, respectively.
(Right) Mitochondrial ROS stained by DHE staining (red) are colocalized with mitochondria (green).
Mitochondria-associated degradation (MAD)
The crosstalk of mitochondrial proteostasis and dynamics
Different mitochondrial quality control pathways, including mitochondrial fission-fusion, movement, and mitophagy interact with each other. We use Drosophila as one of the model system to directly visualize mitochondrial dynamics in intact neurons. We will focus on how mitochondrial proteostasis interacts with mitochondrial dynamics, and the roles of the interaction of different mitochondrial pathways in aging and stress resistance.
Mitochondrial transport in motor neurons in Drosophila larvae
Mitochondria in motor neurons in the segmental nerves in Drosophila larvae
The relative contributions of mitochondrial quality control pathways during the aging process
Deletion of genes involved in mitochondrial quality control pathways results in reduced lifespan in yeast, but the specific effects on lifespan depend on the pathway and experimental conditions. We reveal that MAD is the major pathway acting to promote mitochondrial quality under conditions of chronic, low-level oxidative stress. This raises the possibility that different mitochondrial quality control pathways act during different stages of aging. We will develop novel methods to visualize mitochondrial quality control pathways during the aging process, and determine the relative contributions of mitochondrial quality control during this process.