Interdependence of cytosolic and mitochondrial calcium dynamics in a hepatocyte cell due to obesity

The intentional placement of mitochondria in close proximity to calcium ion (Ca²⁺) release sites enables the quick uptake of cytosolic Ca²⁺ and the close connection of calcium signaling with energy metabolism. Ca²⁺ dynamics have been thoroughly investigated in various cells, including hepatocytes. However, little is known about the interaction between cytosolic and mitochondrial Ca²⁺ dynamics and how it affects adenosine triphosphate (ATP) hydrolysis and nicotinamide adenine dinucleotide (hydrogen) (NADH) production downstream, especially in pathological conditions such as obesity. In this study, we introduce a new reaction-diffusion model of hepatocyte cells that accurately depicts the linked dynamics of mitochondrial and cytosolic Ca²⁺ in both normal and obese states. Important physiological processes, including intracellular buffering, mitochondrial calcium uniporters, Na⁺/Ca²⁺ exchangers, and Ca²⁺ input sources, are integrated into the model. For precise numerical simulations, a combination of the Crank-Nicolson scheme and a linear finite element approach is used. The results show that obese hepatocytes differ significantly from normal cells in terms of calcium signaling, ATP hydrolysis rates, and NADH production. These findings may help guide future experimental and therapeutic research aimed at metabolic liver illnesses and offer fresh insights into how obesity-induced deregulation of calcium dynamics affects cellular energy metabolism.