Research Interests
Regulation of Mitochondrial Biogenesis
Cells make the right amount of mitochondria in response to changes in the quality of carbon sources and to the fincational state of mitochondria.
When grown in glucose media, yeast cells use fermentation to genertae ATP and mitochondria biogenesis is suppressed. When cells switch from fermentation to respiratory growth, mitochondrial biogenesis is stimulated to meet the cellular demand of ATP production. On the other hand, when cells are deficient in respiration, for example, in rho0 cells that have lost mitochondrial DNA, mitochondrial biogenesis is also inhibited. We are studying the mechanisms by which cells make appropriate amounts of mitochondria in response to changes in extracellular and intracellular environments.
Ssy1-Ptr3-Ssy5 (SPS) Amino Acid Sensing
The SPS amino acid-sensing pathway in yeast activates expression of amino acid transporters in response to stimuli of extracellular amino acids. Yeast cells can detect the presence of external amino acids and activate expression of a number of amino acid permeases. In yeast, this system, termed the Ssy1-Ptr3-Ssy5 (SPS) amino acid-sensing pathway, includes Ssy1, a plasma membrane-localized sensor for extracellular amino acids, and two downstream factors, Ptr3 and Ssy5. Ssy5 is a novel protease, whose activation leads to endoproteolytic processing and activation of two zinc-finger transcription factors Stp1/2. Two isoforms of the casein kinase I protein, Yck1 and Yck2, function as positive regulators of this pathway, while protein phosphatase 2A (PP2A) negatively regulates SPS signaling. Grr1, a component of the SCFGrr1 E3 ubiquitin ligase, is also required for activation of SPS signaling. A key activation step in the regulation of SPS signaling is Ssy5-dependent processing of Stp1 and Stp2. Ssy5 undergoes endoproteolytic processing to generate an N-terminal pro-domain and a C-terminal activity domain. It has been shown that proteasome-dependent degradation of the pro-domain of Ssy5 leads to activation of the activity domain. Results in our lab suggested that Ssy5 activation might also be linked to Ptr3 hyperphosphorylation. Liu lab is interested in understanding the molecular mechanisms underlying amino acid sensing and signaling.
Acetic Acid Stress Responses
Weak acids, such as acetic acid, have long been used for food preservation by slowing down the growth of fungal species. In the biofuel industry, acetic acid in the lignocellulosic hydrolysates limits the production of ethanol, which is undesirable. Haa1 is a transcription factor that adapts Saccharomyces cerevisiae cells to weak organic acid stresses by activating the expression of various genes. Many of these genes encode membrane proteins, such as TPO2 and YRO2. By understanding how Haa1 is regulated, researchers can make advances in the field of food sciences to better preserve food and engineer acetic acid-resistant strains that will increase productivity in the biofuel industry. We recently reported that Casein kinase I protein Hrr25 is an important regulator of Haa1 activity. We are currently studying the regulation of Haa1 by other protein kinases.