Unraveling the roles of PLIN5: linking cell biology to physiology

Mason, Rachael R.; Watt, Matthew James

doi:10.1016/j.tem.2015.01.005

Cited by 70 publications

(61 citation statements)

References 78 publications

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“…Such regulation matches fatty acid supply to the prevailing energetic requirements of the cell and thereby protects cells from lipotoxic stress (21,25,26). PLIN5 might also be involved in regulating the interactions between lipid droplets and mitochondria, and in doing so, promote efficient transfer of stored lipids for oxidation (45).…”

Section: Discussionmentioning

confidence: 99%

“…PLIN5 protein content is increased in response to both acute exercise and chronic training (26), and cross-sectional studies report marked upregulation of PLIN5 in endurancetrained athletes compared with sedentary individuals (20). In addition, PLIN5 is localized to the mitochondria (2,24) and appears to remodel the spatial relationship between LDs and the mitochondria and thereby facilitate enhanced contact between these organelles (23,24).…”

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confidence: 99%

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Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training

Mohktar

Montgomery

Murphy

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Mohktar RA, Montgomery MK, Murphy RM, Watt MJ. Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training. Am J Physiol Endocrinol Metab 311: E128 -E137, 2016. First published May 17, 2016; doi:10.1152/ajpendo.00084.2016.-Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5 MKO ), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5 MKO mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5 MKO mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training. perilipin 5; mitochondrial; lipid metabolism; triglyceride CYTOSOLIC LIPID DROPLETS STORE VAST QUANTITIES of triglycerides and are thereby important energy depots in most tissues, including high-energy-consuming tissues such as the liver, heart, and skeletal muscle. Lipid droplets are a central reservoir for fatty acid trafficking, and at least in skeletal muscle, most of the fatty acids that enter the myocyte are first stored as triglycerides within the lipid droplet before being hydrolyzed for oxidation or incorporation into other lipid pools (4,18,27). Such regulation serves the major purposes of supplying fatty acid substrate to match the energetic demands of the tissue and to provide a reservoir for lipid storage, which protects the myocyte from lipotoxic stress and cell death under conditions of excessive lipid flux.Lipid droplets are coated by a multitude of proteins (51) that work in a coordinated manner to regulate cellular ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training

Mohktar

Montgomery

Murphy

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

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“…Under basal condition, Plin1 forms a protective barrier on LDs, preventing lipases from accessing LDs (Brasaemle et al, 2000;Martinez-Botas et al, 2000;Tansey et al, 2001). Plin2 and Plin5 also play similar roles to that of Plin1 (Kimmel and Sztalryd, 2016;Mason et al, 2014;Mason and Watt, 2015;Sztalryd and Kimmel, 2014). In addition, Plin1 interacts with CGI-58, rendering low ATGL activity in hydrolyze TAG Yamaguchi et al, 2004).…”

Section: Ld Degradation By Neutral Lipasesmentioning

confidence: 95%

“…Dysregulated LD homeostasis is closely connected to many pathological conditions and the development of various diseases reactive oxygen species (ROS). peroxisome, organelles responsible for lipid oxidation, also have close association with LDs, and Plin5 has been identified to mediate the interaction between LD and mitochondria and may facilitate the transport of FA for oxidative phosphorylation with increased energy demand (Gao and Goodman, 2015;Lodhi and Semenkovich, 2014;Mason and Watt, 2015;Pu et al, 2011;Rambold et al, 2015;Schrader, 2001;Yu et al, 2015). LDs are also observed surrounding the nucleus or actually present in the nucleus that may function to store specific proteins or sequester transcriptional factors Welte, 2015).…”

Section: The Structure and Function Of Ldsmentioning

confidence: 99%

The size matters: regulation of lipid storage by lipid droplet dynamics

2016

Sci. China Life Sci.

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Adequate energy storage is essential for sustaining healthy life. Lipid droplet (LD) is the subcellular organelle that stores energy in the form of neutral lipids and releases fatty acids under energy deficient conditions. Energy storage capacity of LDs is primarily dependent on the sizes of LDs. Enlargement and growth of LDs is controlled by two molecular pathways: neutral lipid synthesis and atypical LD fusion. Shrinkage of LDs is mediated by the degradation of neutral lipids under energy demanding conditions and is controlled by neutral cytosolic lipases and lysosomal acidic lipases. In this review, we summarize recent progress regarding the regulatory pathways and molecular mechanisms that control the sizes and the energy storage capacity of LDs.

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“…There has been intense interest in the past few years regarding the role of PLIN5 in lipolysis of triacylglycerol from droplets (reviewed in Mason and Watt, 2015). The consensus is that PLIN5 normally serves as a barrier to lipolysis.…”

Section: Plin5 and Fatty Acid Fluxmentioning

confidence: 99%

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

2017

Frontiers Research Topics

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Unraveling the roles of PLIN5: linking cell biology to physiology

Cited by 70 publications

References 78 publications

Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training

Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training

The size matters: regulation of lipid storage by lipid droplet dynamics

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

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