Perilipin 5, lipid droplet-associated protein provides physical and metabolic linkage to mitochondria
ABSTRACT Maintaining cellular lipid homeostasis is crucial to oxidative tissues, and it becomes compromised in obesity. Lipid droplets (LD) play a central role in lipid homeostasis by mediating fatty acid (FA) storage in the form of triglyceride, thereby lowering intracellular levels of lipids that mediate cellular lipotoxicity. LDs and mitochondria have interconnected functions, and anecdotal evidence suggests they physically interact. However, the mechanisms of interaction have not been identified. Perilipins are LD-scaffolding proteins and potential candidates to play a role in their interaction with mitochondria. We examined the contribution of LD perilipin composition to the physical and metabolic interactions between LD and mitochondria using multiple techniques: confocal imaging, electron microscopy (EM), and lipid storage and utilization measurements. Using neonatal cardiomyocytes, reconstituted cell culture models, and rodent heart tissues, we found that perilipin 5 (Plin5) recruits mitochondria to the LD surface through a C-terminal region. Compared with control cells, Plin5-expressing cells show decreased LD hydrolysis, decreased palmitate β-oxidation, and increased palmitate incorporation into triglycerides in basal conditions, whereas in stimulated conditions, LD hydrolysis inhibition is lifted and FA released for β-oxidation. These results suggest that Plin5 regulates oxidative LD hydrolysis and controls local FA flux to protect mitochondria against excessive exposure to FA during physiological stress.
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- "PLIN5 is not only localized in the cytosol and at the surface of LDs; it also associates with mitochondria. Among perilipin, PLIN5 have indeed the distinctive property of recruiting mitochondria at the LD surface . The role of PLIN5 in LD-mitochondrial FA shuttling is a matter of debate and requires further studies  "
ABSTRACT: Cytosolic lipid droplets are dynamic lipid-storage organelles that play a crucial role as reservoirs of metabolic energy and membrane precursors. These organelles are present in virtually all cell types, from unicellular to pluricellular organisms. Despite similar structural organization, lipid droplets are heterogeneous in morphology, distribution and composition. The protein repertoire associated to lipid droplet controls the organelle dynamics. Distinct structural lipid droplet proteins are associated to specific lipolytic pathways. The role of these structural lipid droplet-associated proteins in the control of lipid droplet degradation and lipid store mobilization is discussed. The control of the strictly-regulated lipolysis in lipid-storing tissues is compared between mammals and plants. Differences in the cellular regulation of lipolysis between lipid-storing tissues and other cell types are also discussed. Copyright © 2015. Published by Elsevier B.V.Biochimie 07/2015; DOI:10.1016/j.biochi.2015.07.010 · 2.96 Impact Factor
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- "LD monolayer surface is composed of crucial proteins such as perilipins that determine LD interactions and dynamics (Bickel et al., 2009; Olofsson et al., 2008). In particular, Perilipin 5 (Plin5) is a LD protein that plays a key role in metabolic and physical inter-organelle interactions of LDs and mitochondria in the myocardium (Kuramoto et al., 2012; Wang et al., 2011). These authors proposed that Plin5 regulates the delivery of FA from LD to mitochondria, protecting the mitochondria against an excessive FA supply. "
ABSTRACT: Plasma lipoproteins are a source of lipids for the heart, and the proportion of electronegative low density lipoprotein [LDL(-)] is elevated in cardiometabolic diseases. Perilipin 5 (Plin5) is a crucial protein for lipid droplet management in the heart. Our aim was to assess the effect of LDL(-) on intracellular lipid content and Plin5 levels in cardiomyocytes and to determine whether these effects were influenced by hypoxia. HL-1 cardiomyocytes were exposed to native LDL [LDL(+)], LDL(-), and LDL(+) enriched in non-esterified fatty acids (NEFA) by phospholipase A2 (PLA2)-mediated lipolysis [PLA2-LDL(+)] or by NEFA loading [NEFA-LDL(+)] under normoxia or hypoxia. LDL(-), PLA2-LDL(+) and NEFA-LDL(+) raised the intracellular NEFA and triglyceride (TG) content of normoxic cardiomyocytes. Plin5 was moderately upregulated by LDL(+) but more highly upregulated by LDL(-), PLA2-LDL(+) and NEFA-LDL(+) in normoxic cardiomyocytes. Hypoxia enhanced the effect of LDL(-), PLA2-LDL(+) and NEFA-LDL(+) on intracellular TG and NEFA concentrations but, in contrast, counteracted the upregulatory effect of these LDLs on Plin5. Fluorescence microscopy experiments showed that hypoxic cardiomyocytes exposed to LDL(-), PLA2-LDL(+) and NEFA-LDL(+) have an increased production of reactive oxygen species (ROS). By treating hypoxic cardiomyocytes with WY-14643 (PPARα agonist), Plin5 remained high. In this situation, LDL(-) failed to enhance intracellular NEFA concentration and ROS production. In conclusion, these results show that Plin5 deficiency in hypoxic cardiomyocytes exposed to LDL(-) dramatically increases the levels of unpacked NEFA and ROS. Copyright © 2015. Published by Elsevier Ltd.The international journal of biochemistry & cell biology 06/2015; 65. DOI:10.1016/j.biocel.2015.06.014 · 4.05 Impact Factor
- "An intriguing question is how do mitochondria and LDs interact to regulate lipid metabolism. A recent paper suggests that another member of the plin family, plin5, which is found in oxidative tissue such as brown adipose tissue and skeletal, and cardiac muscle, may recruit mitochondria to the LD (Wang et al, 2011). The identification of OPA1 initiates a new frontier in LD biology and also raises new questions. "