Liver anatomy plays a vital role in its metabolic functions. Hepatocytes in the liver are organized in hexagonal units called lobules. Within each lobule, blood flows directionally from the corners of the hexagon resulting in gradients of nutrients, oxygen, and hormones along the periportal–pericentral axis. These gradients, in turn, drive spatially distinct gene expression that drives the spatial separation of metabolic functions, a phenomenon known as liver zonation. Despite liver zonation being identified over a century ago, factors that govern this spatial heterogeneity are not fully understood. Even less explored is the impact of liver zonation on liver disease and cancer (Cunningham and Porat-Shliom Front Physiol 2021). Mitochondria serve as the cellular metabolic hub, continuously adjusting their metabolic output depending on environmental cues. However, how liver zonation affects mitochondrial functions is largely unexplored.

Our team investigates the fascinating relationship between liver anatomy and metabolism using murine models and human samples. We perturb hepatic functions using genetic, hormonal, and dietary manipulation and investigate mitochondria responses at the cellular, tissue, and organism levels.