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      Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria.

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          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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          Author and article information

          Journal
          J Lipid Res
          Journal of lipid research
          American Society for Biochemistry & Molecular Biology (ASBMB)
          1539-7262
          0022-2275
          Dec 2011
          : 52
          : 12
          Affiliations
          [1 ] The Geriatric Research, Education and Clinical Center, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201.
          [2 ] The Geriatric Research, Education and Clinical Center, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201; Baltimore Veterans Affairs Health Care Center, Division of Endocrinology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201.
          [3 ] VAMHCS Blood/Tissue Banks and Hematology, Division of Pathology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201.
          [4 ] Department of Anesthesiology and the Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland 21201.
          [5 ] Department of Medicine, Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland 21201.
          [6 ] The Geriatric Research, Education and Clinical Center, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201; Baltimore Veterans Affairs Health Care Center, Division of Endocrinology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201. Electronic address: csztalry@grecc.umaryland.edu.
          Article
          S0022-2275(20)40820-X
          10.1194/jlr.M017939
          3220284
          21885430
          7a0a0580-0661-4ed1-bc5f-780cd05b29a9
          History

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