Compartmentalization, cooperation, and communication: The 3Cs of Hepatocyte zonation

Porat-Shliom, Natalie

doi:10.1016/j.ceb.2023.102292

Cited by 1 publication

(2 citation statements)

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“…Advances in omics approaches and microscopy technologies have opened up new avenues for research and discoveries in hepatic cell biology 10 , 11 . Although liver zonation was described nearly a century ago, we are only now starting to unravel how liver anatomy and the gradient of factors within it affect liver function at the tissue level.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, the hepatocytes are exposed to different levels of regional metabolites and metabolic burdens depending on their relative location within the lobule 9 , 10 . It has been previously shown that these gradients direct hepatocytes in different parts of the lobule to express different genes, a phenomenon known as liver zonation 10 , 11 . Wnt ligands secreted by PC endothelial cells are a major driver of zonal gene expression 12 – 14 .…”

Section: Introductionmentioning

confidence: 99%

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A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling

Kang,

Cunningham,

Miller

et al. 2024

Nat Commun

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In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal and pericentral axis. How the mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combine intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We find that periportal and pericentral mitochondria are morphologically and functionally distinct; beta-oxidation is elevated in periportal regions, while lipid synthesis is predominant in the pericentral mitochondria. In addition, comparative phosphoproteomics reveals spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifts mitochondrial phenotypes in the periportal and pericentral regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.

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Section: Discussionmentioning

confidence: 99%