Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Najt, Charles P.; Adhikari, Santosh; Heden, Timothy D.; Cui, Wenqi; Gansemer, Erica R.; Rauckhorst, Adam J.; Markowski, Todd W.; Higgins, LeeAnn; Kerr, Evan W; Boyum, Matthew D; Alvarez, Jonas; Brunko, Sophia; Mehra, Dushyant; Puchner, Elias M.; Taylor, Eric B.; Mashek, Douglas G.

doi:10.1016/j.celrep.2023.112435

Cited by 14 publications

(1 citation statement)

References 95 publications

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“…Proximity to the ER abets the creation of lipid droplets and, as had been suggested, PLIN5 anchors the lipid droplet to these mitochondria. Najt et al [18] used a proteomics approach to show that in hepatocytes, mitochondria in proximity to LDs are enriched in enzymes that drive lipid droplet formation, whereas those in the cytosol are enriched with enzymes associated with fatty acid oxidation. Using isotope tracing, they went on to show that fasting routed more fatty acids to the cytosolic mitochondria and promoted lipophagy.…”

Section: Regulation Of Lipid Droplet Formationmentioning

confidence: 99%

Intracellular lipase and regulation of the lipid droplet

Cabodevilla,

Son,

Goldberg

2024

Current Opinion in Lipidology

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Purpose of review Lipid droplets are increasingly recognized as distinct intracellular organelles that have functions exclusive to the storage of energetic lipids. Lipid droplets modulate macrophage inflammatory phenotype, control the availability of energy for muscle function, store excess lipid, sequester toxic lipids, modulate mitochondrial activity, and allow transfer of fatty acids between tissues. Recent findings There have been several major advances in our understanding of the formation, dissolution, and function of this organelle during the past two years. These include new information on movement and partition of amphipathic proteins between the cytosol and lipid droplet surface, molecular determinants of lipid droplet formation, and pathways leading to lipid droplet hydrophobic lipid formation. Rapid advances in mitochondrial biology have also begun to define differences in their function and partnering with lipid droplets to modulate lipid storage versus oxidation. Summary This relationship of lipid droplets biology and cellular function provides new understanding of an important cellular organelle that influences muscle function, adipose lipid storage, and diseases of lipotoxicity.

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Section: Regulation Of Lipid Droplet Formationmentioning

confidence: 99%

Intracellular lipase and regulation of the lipid droplet

Cabodevilla,

Son,

Goldberg

2024

Current Opinion in Lipidology

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Molecular mechanisms of perilipin protein function in lipid droplet metabolism

Griseti,

Bello,

Bieth

et al. 2024

FEBS Letters

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Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino‐terminal PAT domain and an 11‐mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy‐terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.

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Functional interplay of lipid droplets and mitochondria

Enkler,

Spang

2024

FEBS Letters

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Our body stores energy mostly in form of fatty acids (FAs) in lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes and mitochondria. This transfer is dependent on close opposition of LDs and mitochondria and peroxisomes and happens at membrane contact sites. However, the composition and the dynamics of these contact sites is not well understood, which is in part due to the dependence on the metabolic state of the cell and on the cell‐ and tissue‐type. Here, we summarize the current knowledge on the contacts between lipid droplets and mitochondria both in mammals and in the yeast Saccharomyces cerevisiae, in which various contact sites are well studied. We discuss possible functions of the contact site and their implication in disease.

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Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Cited by 14 publications

References 95 publications

Intracellular lipase and regulation of the lipid droplet

Intracellular lipase and regulation of the lipid droplet

Molecular mechanisms of perilipin protein function in lipid droplet metabolism

Functional interplay of lipid droplets and mitochondria

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