Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver
Abstract
Mitochondria-associated endoplasmic reticulum membranes (MAM) play a key role in mitochondrial dynamics and function and in hepatic insulin action. Whereas mitochondria are important regulators of energy metabolism, the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown. In this study, we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse liver. Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A (PP-PP2A) pathway, induced mitochondria fission, and impaired respiration. Blocking MAM reduction counteracted glucose-induced mitochondrial alterations. Furthermore, disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function. This glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice, both characterized by chronic disruption of MAM integrity, mitochondrial fission, and altered mitochondrial respiration. These data indicate that MAM contribute to the hepatic glucose-sensing system, allowing regulation of mitochondria dynamics and function during nutritional transition. Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance.
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Interaction between mitochondria and ER has been demonstrated in mouse and human primary hepatocytes and in mice.
“The interaction between mitochondria and ER has been demonstrated in mouse and human primary hepatocytes and in mice (Tubbs et al., 2014; Theurey et al., 2016).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Theurey et al., 2016
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- Authors
- Theurey, P., Tubbs, E., Vial, G., Jacquemetton, J., Bendridi, N., Chauvin, M.-A., Alam, M. R., Le Romancer, M., Vidal, H., & Rieusset, J.
- Affiliations
- Lyon 1 Université (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Rieusset, Jennifer
- ORCID
- Venue
- Journal of Molecular Cell Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-17
- Volume
- 8
- Issue
- 2
- Pages
- 129-143
- ISSN
- 1674-2788 (ISSN-L)
- 1759-4685
- OpenAlex
- W2302578324
- Cited by
- 175
- References
- 39
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 13 · 2023: 21 · 2022: 24 · 2021: 16 · 2020: 23 · 2019: 19 · 2018: 17 · 2017: 13 · 2016: 3
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- INSERM, the national research agency (ANR-09-JCJC-0116)
- French government of higher education and research
- Fondation pour la Recherche Médicale (FDT20140931004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondria-associated endoplasmic reticulum membranes, glucose detection, hepatic glucose metabolism, mitochondrial dynamics, mitochondrial fission, mitochondrial respiration, pentose phosphate pathway, protein phosphatase 2A, insulin resistance, ob/ob mice, cyclophilin D
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Endoplasmic Reticulum, Glucose, Humans, Intracellular Membranes, Liver, Mitochondria, Nutritional Status, Phosphoprotein Phosphatases, Signal Transduction, Mice, Knockout, Postprandial Period, Hepatocytes, Voltage-Dependent Anion Channel 1, Mice, Inositol 1,4,5-Trisphosphate Receptors
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