Search bioRxiv⌕ Search

Biology subjects

Mukherji, S.

Publications and source records attributed to Mukherji, S..

5 recordsLinked to original sources

Multiplexed quantum sensing reveals coordinated thermomagnetic regulation of mitochondria

Mitochondria are multifunctional organelles that convert the potential energy stored in nutrients and intermediary metabolites into both heat and an electrochemical proton-motive force. However, how these outputs are synchronized in cells remains an enduring question. In this work, leveraging multiplexed nanodiamond quantum sensors to monitor both changes in temperature and magnetic field fluctuations in single primary cells obtained from diverse tissues in adult mice, we identified thermomagnetic correlation profiles uncovering a regulatory feedback loop in which the cell draws upon available intracellular iron to maintain the mitochondrial electrochemical gradient. These profiles reverse in cells derived from a mouse model of Leigh syndrome and raise the intriguing possibility that primary mitochondrial diseases can be understood as disorders of thermomagnetic homeostasis.

biophysics↗

The response of mitochondrial position to glucose stimulation in a model system of the pancreatic beta cell

The compartmentalization of eukaryotic cells into membrane-bound organelles with specific subcellular positioning enables precise spatial and temporal control of cellular functions. While functionally significant mitochondrial localization has been demonstrated in cells such as neurons, it remains unclear how general these cell principles are. Here, we examine the spatial organization of mitochondria within MIN6 pancreatic beta cells under variable glucose conditions. We observe glucose-dependent redistributions of mitochondria, favoring peripheral localization at elevated glucose levels when insulin secretion is also elevated. Our results, formalized into a stochastic model of mitochondrial trafficking, suggest that active mitochondrial transport along microtubules and calcium activity, but not ATP synthesis, are critical regulators of this redistribution. These results suggest that mitochondrial positioning may contribute to optimizing energy delivery in response to local demand, potentially representing a general regulatory mechanism across various cell types.

cell biology↗

Competition for resources during development drives allometric patterns in the grass Setaria

Plant growth and resilience is greater than the sum of its component traits, with important traits influencing one another. This interdependency makes it challenging to identify the genetic determinants of key agronomic traits, such as water use efficiency. Measuring traits such as plant height and size is possible via image analysis software, such as PlantCV, but these traits are often highly correlated. Furthermore, plant size is estimated using a 2D projection of a 3D object, which is more difficult for plants with complex body plans. To address these problems, we developed a generalizable, biologically-informed model describing the temporal coordination of semi-sequential phytomeric growth in the model grass Setaria. Our approach integrates time dependence with water usage, the growth of phytomers, and the emergence of side shoots or tillers, improving our ability to estimate both phytomer-level phenotypes and water usage traits in high-throughput. We developed new PlantCV methods to inform the Phytomeric Growth Model, and estimated parameter traits using a high-throughput phenotyping dataset of a recombinant inbred line (RIL) panel in well-watered and drought conditions. Model parameter estimates identified additional quantitative trait loci (QTL) for new traits compared to the directly measured PlantCV-derived estimates, and predicted the relationships underlying QTL control of composite traits through co-localization of model parameters to loci controlling size and water use metrics. The Phytomeric Growth Model estimates improved our ability to estimate the growth of tillers and obtain a model-based estimate of marginal water use efficiency (defined here as the ratio of biomass gained per gram of water transpired), both identified as highly influential on plant drought responses through random forest classification. Our approach demonstrates the value of integrating mechanistic modeling with high-throughput imaging to extract new information at scale.

plant biology↗

Uncovering the principles coordinating systems-level organelle biogenesis with cellular growth

Among the hallmark properties of the eukaryotic cell is its organization into specialized biochemical compartments known as organelles. Understanding how organelle biogenesis at systems-scale is coordinated with cellular growth rate and size is a major goal of quantitative cell biology. Here we map out the correlation structure of systems-level organelle biogenesis with cellular growth using "rainbow yeast", a strain of Saccharomyces cerevisiae that expresses fluorescent labels for 6 major organelles. By carrying out hyperspectral imaging of thousands of single rainbow yeast cells, we decomposed the systems-level organelle biogenesis program into specific modes that characterize the response to changes in nutrient availability. Upon chemical biological dissection of this response, our results suggest that systems-level organelle biogenesis represents the sum of distinct organelle modes excited by growth rate and cell size separately. The flexibility afforded by this regulatory architecture may underlie how eukaryotic cells leverage compartmentalization to independently tune cell sizes and growth rates and satisfy potentially incompatible environmental and developmental constraints.

systems biology↗

Robust organelle size control via bursty growth

One of the grand challenges in quantitative cell biology is understanding the precision with which cells assemble and maintain subcellular organelles. A critical property that governs organelle function is its size. Organelle sizes must be flexible enough to allow cells to grow or shrink them as environments demand, yet be maintained within homeostatic limits. Despite identification of numerous molecular factors that regulate organelle sizes we lack insight into the quantitative principles underlying organelle size control. Here we examine organelle sizes from Saccharomyces cerevisiae and human iPS cells with mathematical theory to show that cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship we predict theoretically, our framework suggests that organelles grow in random bursts from a limited pool of building blocks. Burst-like growth provides a general biophysical mechanism by which cells can maintain on average reliable yet plastic organelle sizes.

systems biology↗