Lipid Droplet-Organelle Contact Sites as Hubs for Fatty Acid Metabolism, Trafficking, and Metabolic Channeling

Renne, Mike F.; Hariri, Hanaa

doi:10.3389/fcell.2021.726261

Cited by 59 publications

(45 citation statements)

References 116 publications

(152 reference statements)

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“…During adipogenic differentiation, the cells retained a high level of metabolic activity and increased substrate consumption along with a marked increase in the mitochondrial content and higher β-oxidation [ 29 ]. Lipid metabolism, including lipid transport, synthesis, and catabolism, requires high levels of energy and fully functional mitochondria, and the normal function of complex I is critical for these processes [ 30 ]. Therefore, it is anticipated that loss of other subunits of complex I will also inhibit adipogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

Ndufa6 regulates adipogenic differentiation via Scd1

et al. 2021

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Obesity and associated complications are becoming a pandemic. Inhibiting adipogenesis is an important intervention for the treatment of obesity. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear, and many potential therapeutic targets have yet to be discovered. Transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenic differentiation and the potential mechanism in OP9 cells and adipose-derived stem cells. In this study, we found that NADH:ubiquinone oxidoreductase subunit A6 ( Ndufa6 ) participates in the regulation of adipogenic differentiation. Furthermore, we show that the effect of Ndufa6 is mediated through stearoyl-CoA desaturase 1 ( Scd1 ) and demonstrate the inhibitory effect of a SCD1 inhibitor on adipogenesis. Our study broadens the understanding of adipogenic differentiation and offers NDUFA6-SCD1 as a potential therapeutic target for the treatment of obesity.

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Section: Discussionmentioning

confidence: 99%

Ndufa6 regulates adipogenic differentiation via Scd1

et al. 2021

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“…As LDs play primary roles in lipid storage and homeostasis 179 , the biogenesis and expansion of LDs, which are regulated by organelle interactions, play significant roles in cellular senescence. It has been shown that LD contact sites play an important role in fatty acid synthesis, storage, release, and breakdown 186 . Inhibition of LD biogenesis during rapid fatty acid release leads to fatty acid-mediated mitochondrial depolarization 81 , which increases the release of mitochondrial ROS 187 , and leads to cellular senescence (Fig.…”

Section: The Role Of Organelle Interaction In Cellular Senescencementioning

confidence: 99%

The relevance of organelle interactions in cellular senescence

Huang¹,

Meng²,

Wang³

et al. 2022

Theranostics

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Organelles are tiny structures with specific functions in eukaryotic cells. Since they are covered with membranes, different organelles can perform biological processes that are incompatible. Organelles can also actively communicate with each other to maintain cellular homeostasis via the vesicular trafficking pathways and membrane contact sites (MCSs), which allow the exchange of metabolites and other information required for normal cellular physiology. An imbalance in organelle interactions may result in multiple pathological processes. Growing evidence shows that abnormal organelle communication contributes to cellular senescence and is associated with organ aging. However, the key role of organelle interactions in aging has not yet been broadly reviewed and fully investigated. In this review, we summarize the role of organelle interactions in cellular senescence, and highlight their relevance for cellular calcium homeostasis, protein and lipid homeostasis, and mitochondrial quality control. Our review reveals important mechanisms of organelle interactions in cellular senescence and provides important clues for intervention strategies from a new perspective.

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“…LDs are also connected to peroxisomes to relieve LDs from damage induced through lipid peroxidation ( Chang et al, 2019 ). Some of the proteinaceous machineries and the associated molecular mechanisms involved in the formation, maintenance and dynamics of these other LD-organelle contact sites have been characterized ( Freyre et al, 2019 ; Olzmann and Carvalho, 2019 ; Choudhary and Schneiter, 2021 ; Renne and Hariri, 2021 ).…”

Section: Lipid Droplets and Seipins: Desorbing Lipids Between Bi- And Mono- Layersmentioning

confidence: 99%

Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels

Egea

2021

Front. Cell Dev. Biol.

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Eukaryotic cells are characterized by their exquisite compartmentalization resulting from a cornucopia of membrane-bound organelles. Each of these compartments hosts a flurry of biochemical reactions and supports biological functions such as genome storage, membrane protein and lipid biosynthesis/degradation and ATP synthesis, all essential to cellular life. Acting as hubs for the transfer of matter and signals between organelles and throughout the cell, membrane contacts sites (MCSs), sites of close apposition between membranes from different organelles, are essential to cellular homeostasis. One of the now well-acknowledged function of MCSs involves the non-vesicular trafficking of lipids; its characterization answered one long-standing question of eukaryotic cell biology revealing how some organelles receive and distribute their membrane lipids in absence of vesicular trafficking. The endoplasmic reticulum (ER) in synergy with the mitochondria, stands as the nexus for the biosynthesis and distribution of phospholipids (PLs) throughout the cell by contacting nearly all other organelle types. MCSs create and maintain lipid fluxes and gradients essential to the functional asymmetry and polarity of biological membranes throughout the cell. Membrane apposition is mediated by proteinaceous tethers some of which function as lipid transfer proteins (LTPs). We summarize here the current state of mechanistic knowledge of some of the major classes of LTPs and tethers based on the available atomic to near-atomic resolution structures of several “model” MCSs from yeast but also in Metazoans; we describe different models of lipid transfer at MCSs and analyze the determinants of their specificity and directionality. Each of these systems illustrate fundamental principles and mechanisms for the non-vesicular exchange of lipids between eukaryotic membrane-bound organelles essential to a wide range of cellular processes such as at PL biosynthesis and distribution, lipid storage, autophagy and organelle biogenesis.

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Lipid Droplet-Organelle Contact Sites as Hubs for Fatty Acid Metabolism, Trafficking, and Metabolic Channeling

Cited by 59 publications

References 116 publications

Ndufa6 regulates adipogenic differentiation via Scd1

Ndufa6 regulates adipogenic differentiation via Scd1

The relevance of organelle interactions in cellular senescence

Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels

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