Biology subjects

Hua, B.

Publications and source records attributed to Hua, B..

3 recordsLinked to original sources

bioRxiv2018

Circadian gene Clock regulates mitochondrial morphology and functions by posttranscriptional way

Many daily activities are under the control of circadian clock, including nutrition metabolism and energy generation. Mitochondria, as the core factories of oxidizing substrates and producing ATP, undergo changes in quantity and morphology to adapt to the demand for energy. It has been demonstrated that mitochondrial gene expression, dynamics and functions are all affected by circadian clock. Here, we demonstrated that circadian gene Clock affects the number, architecture and function of mitochondria via posttranscriptional regulation of Drp1. Clock{Delta}19 leads to fragmented mitochondria accompanied with the loss of membrane potential, excessive ROS accumulation and decreased mitochondrial respiration and ATP generation. Clock{Delta}19 mice exhibit disordered lipid metabolism and evident nonalcoholic fatty liver disease (NAFLD), which are rescued by treatment with the mitochondrial fission inhibitor Mdivi-1. These results suggest a strong relationship between Clock, mitochondrial dynamics and metabolic diseases and provide a new perspective on disordered circadian clock and related diseases.

cell biology↗

bioRxiv2017

Small effect-size mutations cumulatively affect yeast quantitative traits

SummaryQuantitative traits are influenced by pathways that have traditionally been defined through genes that have a large loss- or gain-of-function effect. However, in theory, a large number of small effect-size genes could cumulative play a substantial role in pathway function, potentially by acting as \"modifiers\" that tune the levels of large effect size pathway components. To understand the role of these small effect-size genes, we used a quantitative assay to determine the number, strength, and identity of all non-essential genes that affect two galactose-responsive (GAL) traits, in addition to re-analyzing two previously screened quantitative traits. Over a quarter of assayed genes have a detectable effect; approximately two thirds of the quantitative trait variation comes from small effect-size genes. The functions of small effect-size genes are partially overlapping between traits and are enriched in core cellular processes. This implies that genetic variation in one process has the potential to influence behavior or disease in seemingly unconnected processes.\n\nHighlightsO_LIFour yeast quantitative traits are affected by thousands of small effect-size genes.\nC_LIO_LISmall effect-size genes are enriched in core cellular processes\nC_LIO_LIThe effects of these genes are quantitative trait-specific.\nC_LI

systems biology↗

bioRxiv2017

Polymorphisms In The Yeast Galactose Sensor Underlie A Natural Continuum Of Nutrient-Decision Phenotypes

In nature, microbes often need to \"decide\" which of several available nutrients to utilize, a choice that depends on a cells inherent preference and external nutrient levels. While natural environments can have mixtures of different nutrients, phenotypic variation in microbes decisions of which nutrient to utilize is poorly studied. Here, we quantified differences in the concentration of glucose and galactose required to induce galactose-responsive (GAL) genes across 36 wild S. cerevisiae strains. Using bulk segregant analysis, we found that a locus containing the galactose sensor GAL3 was associated with differences in GAL signaling in eight different crosses. Using allele replacements, we confirmed that GAL3 is the major driver of GAL induction variation, and that GAL3 allelic variation alone can explain as much as 90% of the variation in GAL induction in a cross. The GAL3 variants we found modulate the diauxic lag, a selectable trait. These results suggest that ecological constraints on the galactose pathway may have led to variation in a single protein, allowing cells to quantitatively tune their response to nutrient changes in the environment.\n\nAuthor summaryIn nature, microbes often need to decide which of many potential nutrients to consume. This decision making process is complex, involving both intracellular constraints and the organisms perception of the environment. To begin to mimic the complexity of natural environments, we grew cells in mixtures of two sugars, glucose and galactose. We find that in mixed environments, the sugar concentration at which cells decides to induce galactose-utilizing (GAL) genes is highly variable in natural isolates of yeast. By analyzing crosses of phenotypically different strains, we identified a locus containing the galactose sensor, a gene that in theory could allow cells to tune their perception of the environment. We confirmed that the galactose sensor can explain upwards of 90% of the variation in the decision to induce GAL genes. Finally, we show that the variation in the galactose sensor can modulate the time required for cells to switch from utilizing glucose to galactose. Our results suggest that signaling pathways can be highly variable across strains and thereby might allow for rapid adaption in fluctuating environments.

genetics↗