Biology subjects

Yamagishi, J. F.

Publications and source records attributed to Yamagishi, J. F..

3 recordsLinked to original sources

bioRxiv2022

Quantitative Relationship between Intracellular Metabolic Responses against Nutrient Conditions and Metabolic Inhibitions

Many previous studies have attempted to predict the metabolic states of cells assuming metabolic regulation is optimized through (sometimes artificial) evolution for some objective, e.g., growth rate or production of some metabolites. Conventional approaches, however, require identifying the microscopic details of individual metabolic reactions and the objective functions of cells, and their predictions sensitively depend on such details. In this study, we focus on the responses of metabolic systems to environmental perturbations, rather than their metabolic states themselves, and theoretically demonstrate a universal property of the responses independent of the systems details. With the help of a microeconomic theory, we show a simple relationship between intracellular metabolic responses against nutrient abundance and metabolic inhibition due to manipulation such as drug administration: these two experimentally measurable quantities show a proportional relationship with a negative coefficient. This quantitative relationship should hold in arbitrary metabolic systems as long as the law of mass conservation holds and cells are optimized for some objectives, but the true objective functions need not be known. Through numerical calculations using large-scale metabolic networks such as the E. coli core model, we confirmed that the relationship is valid from abstract to detailed models. Because the relationship provides quantitative predictions regarding metabolic responses without prior knowledge of systems, our findings have implications for experimental applications in microbiology, systems biology, metabolic engineering, and medicine, particularly for unexplored organisms or cells.

systems biology↗

bioRxiv2020

Microbial Potlatch: Cell-level adaptation of leakiness of metabolites leads to resilient symbiosis among diverse cells

Microbial communities display extreme diversity, facilitated by the secretion of chemicals that can create new niches. However, it is unclear why cells often secrete even essential metabolites after evolution. By noting that cells can enhance their own growth rate by leakage of essential metabolites, we show that such leaker cells can benefit from coexistence with cells that consume the leaked chemicals in the environment. This leads to an unusual form of mutualism between "leaker" and "consumer" cells, resulting in frequency-dependent coexistence of multiple microbial species, as supported by extensive simulations. Remarkably, such symbiotic relationships generally evolve when each species adapts its leakiness to optimize its own growth rate under crowded conditions and nutrient limitations, leading to ecosystems with diverse species exchanging many metabolites with each other. In addition, such ecosystems are resilient against structural and environmental perturbations. Thus, we present a new basis for diverse, complex microbial ecosystems.

ecology↗

bioRxiv2019

Microeconomics of metabolism: Overflow metabolism as Giffen behavior

Biological systems such as intracellular metabolism are rationally regulated to maximize the cellular growth rate through evolution (1-4), whereas microeconomics investigates the behaviour of consumers assumed to rationally maximize their utility (5, 6). Despite this analogy as optimization problems, the link between biology and economics has not been fully established (7, 8). Here, we developed an exact mapping between the regulation of metabolism and the theory of consumer choice, thereby revealing the correspondence between long-standing mysteries in both fields: overflow metabolism and Giffen behaviour. Overflow metabolism, particularly known as the Warburg effect in cancer (9, 10), is a seemingly wasteful but ubiquitous strategy where cells utilize aerobic glycolysis instead of the more energetically-efficient oxidative phosphorylation (9-16), whereas Giffen behaviour is the unexpected consumer behaviour where a good is demanded more as its price rises (17, 18). We revealed that the general conditions for these phenomena are trade-off and complementarity, i.e., impossibility of substitution for different goods. This correspondence implies that oxidative phosphorylation is counterintuitively stimulated when its efficiency is decreased by metabolic perturbations like drug administration. Therefore, Giffen behaviour bridges the Warburg effect and the reverse and inverse Warburg effect (19-22). This highlights that application of microeconomics to metabolism can offer new predictions and paradigms for both biology and economics.

systems biology↗