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PMID:21885430

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Citation

Wang, H, Sreenivasan, U, Sreenevasan, U, Hu, H, Saladino, A, Polster, BM, Lund, LM, Gong, DW, Stanley, WC and Sztalryd, C (2011) Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J. Lipid Res. 52:2159-68

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.

Links

PubMed PMC3220284 Online version:10.1194/jlr.M017939

Keywords

Amino Acid Sequence; Animals; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Cattle; Cell Line; Humans; Hydrolysis; Lipid Metabolism; Lipids/chemistry; Male; Mice; Mitochondria/metabolism; Molecular Sequence Data; Oxidation-Reduction; Palmitates/metabolism; Protein Structure, Tertiary; Rats; Triglycerides/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:PLIN5

located_in

GO:0005811: lipid droplet

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:PLIN5

NOT|colocalizes_with

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PLIN5

involved_in

GO:0010867: positive regulation of triglyceride biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLIN5

involved_in

GO:0031999: negative regulation of fatty acid beta-oxidation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLIN5

involved_in

GO:0050995: negative regulation of lipid catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLIN5

involved_in

GO:0051646: mitochondrion localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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