The Membrane Lipid Phosphatidylcholine Is an Unexpected Source of Triacylglycerol in the Liver

Veen, Jelske N. van der; Lingrell, Susanne; Vance, Dennis E.

doi:10.1074/jbc.m112.381723

Cited by 61 publications

(60 citation statements)

References 39 publications

(29 reference statements)

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“…Transport of lipids from OMM to IMM may occur either by membrane contact or by translocation through the intermembrane space. Despite its role in IMM organization the cristae-forming MINOS complex (Harner et al 2011;Hoppins et al 2011;van der Laan et al 2012) is most likely not involved in this process. The role of Gem1p and Ups-proteins in OMM-IMM lipid translocation has to be taken into account (Tamura et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…This IMM-associated complex functions in cristae formation and morphology (Rabl et al 2009). It was proposed (van der Laan et al 2012) that MINOS forms the central core of a large and complex organizing system named ERMIONE, which includes the ERMES complex, the prohibitin ringlike structures, the TOM and TIM complexes, and Mdm31/32 proteins required for mtDNA maintenance. MINOS was also found to interact with the protein VDAC and with the fusion protein Ugo1 (van der Laan et al 2012).…”

Section: Vv Flis and G Daummentioning

confidence: 99%

“…It was proposed (van der Laan et al 2012) that MINOS forms the central core of a large and complex organizing system named ERMIONE, which includes the ERMES complex, the prohibitin ringlike structures, the TOM and TIM complexes, and Mdm31/32 proteins required for mtDNA maintenance. MINOS was also found to interact with the protein VDAC and with the fusion protein Ugo1 (van der Laan et al 2012). Both ERMES and MINOS are genetically linked to the prohibitin ring complexes of the IMM that are integrated into the lipid network metabolism (Psd1, Ups1/Ups2) (Birner et al 2003;Gohil et al 2005;Kornmann et al 2009;Osman et al 2009a;Tamura et al 2009Tamura et al , 2012Potting et al 2010).…”

Section: Vv Flis and G Daummentioning

confidence: 99%

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Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Flis

Daum

2013

Cold Spring Harbor Perspectives in Biology

160

124

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Mitochondria are partially autonomous organelles that depend on the import of certain proteins and lipids to maintain cell survival and membrane formation. Although phosphatidylglycerol, cardiolipin, and phosphatidylethanolamine are synthesized by mitochondrial enzymes, phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and sterols need to be imported from other organelles. The origin of most lipids imported into mitochondria is the endoplasmic reticulum, which requires interaction of these two subcellular compartments. Recently, protein complexes that are involved in membrane contact between endoplasmic reticulum and mitochondria were identified, but their role in lipid transport is still unclear. In the present review, we describe components involved in lipid translocation between the endoplasmic reticulum and mitochondria and discuss functional as well as regulatory aspects that are important for lipid homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Vv Flis and G Daummentioning

confidence: 99%

Section: Vv Flis and G Daummentioning

confidence: 99%

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Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Flis

Daum

2013

Cold Spring Harbor Perspectives in Biology

160

124

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“…However, this pathway is essential for the generation of specific molecular species of PC. In addition to the CDP-choline pathway, another important source of hepatic PC comes from lipoproteins [77].…”

Section: Reduced Phosphatidylcholine Levelsmentioning

confidence: 99%

Acid sphingomyelinase-ceramide system in steatohepatitis: A novel target regulating multiple pathways

Garcı́a-Ruiz

Mato

Vance

et al. 2015

Journal of Hepatology

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Steatohepatitis (SH) is an intermediate stage of fatty liver disease and is one of the most common causes of chronic liver disease worldwide that may progress to cirrhosis and liver cancer. SH encompasses alcoholic and non-alcoholic steatohepatitis, the latter being of particular concern as it is associated with obesity and insulin resistance and has become a major cause of liver transplantation. The molecular mechanisms governing the transition from steatosis to SH are not fully understood. Here we discuss emerging data indicating that the acid sphingomyelinase (ASMase), a specific mechanism of ceramide generation, is required for the activation of key pathways that regulate steatosis, fibrosis and lipotoxicity, including endoplasmic reticulum stress, autophagy and lysosomal membrane permeabilization. Moreover, ASMase modulates alterations of the methionine cycle and phosphatidylcholine homeostasis, two crucial events involved in SH that regulate methylation reactions, antioxidant defence and membrane integrity. These new findings suggest that targeting ASMase in combination with restoring methionine metabolism and phosphatidylcholine levels may be of utility in the treatment of SH.

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“…Phosphatidylcholine (PC) is the main circulating phospholipid and is mostly found on HDL particles; it plays a role in the regulation of circulating lipoprotein levels, especially VLDL (7). Plasma PC levels were found to be altered in the obese state and may be involved in obesity-related hepatic steatosis (49). Sun et al (43) observed high blood PC levels as well as elevated cholesterol and triglyceride concentrations in pigs fed a high-fat diet without weight gain compared with animals fed a control diet.…”

mentioning

confidence: 99%

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

Boulet

Chevrier

Grenier-Larouche

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

108

105

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profiling of obese individuals revealed altered concentrations of many metabolites, especially branched-chain amino acids (BCAA), possibly linked to altered adipose tissue BCAA catabolism. We tested the hypothesis that some features of this metabolite signature relate closely to visceral obesity and concomitant alterations in cardiometabolic risk factors. We also postulated that alterations in BCAA-catabolizing enzymes are predominant in visceral adipose tissue. Fifty-nine women (BMI 20 -41 kg/m 2 ) undergoing gynecologic surgery were recruited and characterized for overall and regional adiposity, blood metabolite levels using targeted metabolomics, and cardiometabolic risk factors. Adipose samples (visceral and subcutaneous) were obtained and used for gene expression and Western blot analyses. Obese women had significantly higher circulating BCAA and kynurenine/tryptophan (Kyn/Trp) ratio than lean or overweight women (P Ͻ 0.01). Principal component analysis confirmed that factors related to AA and the Kyn/Trp ratio were positively associated with BMI, fat mass, visceral or subcutaneous adipose tissue area, and subcutaneous adipocyte size (P Յ 0.05). AA-related factor was positively associated with HOMA-IR (P Յ 0.01). Factors reflecting glycerophospholipids and sphingolipids levels were mostly associated with altered blood lipid concentrations (P Յ 0.05). Glutamate level was the strongest independent predictor of visceral adipose tissue area (r ϭ 0.46, P Ͻ 0.001). Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue than overweight or lean women (P Յ 0.05). We conclude that among metabolites altered in obesity plasma concentrations of BCAA and the Kyn/Trp ratio are closely related to increased adiposity. Alterations in expression and protein levels of BCAA-catabolizing enzymes are predominant in visceral adipose tissue.

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The Membrane Lipid Phosphatidylcholine Is an Unexpected Source of Triacylglycerol in the Liver

Cited by 61 publications

References 39 publications

Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Acid sphingomyelinase-ceramide system in steatohepatitis: A novel target regulating multiple pathways

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

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