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

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
28 Feb 2024
Historique:
received: 24 04 2023
accepted: 04 02 2024
medline: 29 2 2024
pubmed: 29 2 2024
entrez: 28 2 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-45751-9 PMID: 38418824
pubmed: 38418824
doi: 10.1038/s41467-024-45751-9
pii: 10.1038/s41467-024-45751-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1799

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 1ZIABC011828

Informations de copyright

© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Auteurs

Sun Woo Sophie Kang (SWS)

Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Rory P Cunningham (RP)

Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Colin B Miller (CB)

Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Lauryn A Brown (LA)

Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Constance M Cultraro (CM)

Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Adam Harned (A)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Cancer Research Technology Programs, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Kedar Narayan (K)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Cancer Research Technology Programs, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
ORCID: 0000-0001-7982-6494

Jonathan Hernandez (J)

Surgical Oncology Program, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Lisa M Jenkins (LM)

Laboratory of Cell Biology, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
ORCID: 0000-0003-1245-1338

Alexei Lobanov (A)

CCR Collaborative Bioinformatics Resource (CCBR) National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Maggie Cam (M)

CCR Collaborative Bioinformatics Resource (CCBR) National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Natalie Porat-Shliom (N)

Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. poratshliomn@mail.nih.gov.
ORCID: 0000-0003-2676-8483

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