Proteomic insights into an expanded cellular role for cytoplasmic lipid droplets

Hodges, Brittany D. M.; Wu, Christine C.

doi:10.1194/jlr.r003582

Cited by 142 publications

(161 citation statements)

References 92 publications

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“…Instead, LD‐linked proteins are found to associate through alternative mechanisms (i.e., lipid modifications, hairpin loops, or amphipathic helices4). Numerous proteomic studies have shown that a significant number of Rab family members are consistently associated with the LD monolayer,5, 6, 40, 41, 42, 43, 44 likely through interactions occurring though C‐terminal prenylation sites. Among the Rabs, Rab7 and Rab18 appear to be especially prominent on the LD, as evidenced by their repeated presence in the diverse proteomic analyses listed above.…”

Section: Discussionmentioning

confidence: 99%

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Schulze¹,

Rasineni

Weller³

et al. 2017

Hepatology Communications

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Alcohol consumption is a well‐established risk factor for the onset and progression of fatty liver disease. An estimated 90% of heavy drinkers are thought to develop significant liver steatosis. For these reasons, an increased understanding of the molecular basis for alcohol‐induced hepatic steatosis is important. It has become clear that autophagy, a catabolic process of intracellular degradation and recycling, plays a key role in hepatic lipid metabolism. We have shown that Rab7, a small guanosine triphosphatase known to regulate membrane trafficking, acts as a key orchestrator of hepatocellular lipophagy, a selective form of autophagy in which lipid droplets (LDs) are specifically targeted for turnover by the autophagic machinery. Nutrient starvation results in Rab7 activation on the surface of the LD and lysosomal compartments, resulting in the mobilization of triglycerides stored within the LDs for energy production. Here, we examine whether the steatotic effects of alcohol exposure are a result of perturbations to the Rab7‐mediated lipophagic pathway. Rats chronically fed an ethanol‐containing diet accumulated significantly higher levels of fat in their hepatocytes. Interestingly, hepatocytes isolated from these ethanol‐fed rats contained juxtanuclear lysosomes that exhibited impaired motility. These changes are similar to those we observed in Rab7‐depleted hepatocytes. Consistent with these defects in the lysosomal compartment, we observed a marked 80% reduction in Rab7 activity in cultured hepatocytes as well as a complete block in starvation‐induced Rab7 activation in primary hepatocytes isolated from chronic ethanol‐fed animals. Conclusion: A mechanism is supported whereby ethanol exposure inhibits Rab7 activity, resulting in the impaired transport, targeting, and fusion of the autophagic machinery with LDs, leading to an accumulation of hepatocellular lipids and hepatic steatosis. (Hepatology Communications 2017;1:140‐152)

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Section: Discussionmentioning

confidence: 99%

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Schulze¹,

Rasineni

Weller³

et al. 2017

Hepatology Communications

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“…The results are discussed in detail in a recent review (Hodges et al 2009). Because of ample lipid ester content, LDs have exceptionally high buoyancy and thus can be easily separated from other organelles.…”

Section: The Lipid Droplet Proteomementioning

confidence: 99%

Not Just Fat: The Structure and Function of the Lipid Droplet

Fujimoto

Parton²

2011

Cold Spring Harbor Perspectives in Biology

409

336

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Lipid droplets (LDs) are independent organelles that are composed of a lipid ester core and a surface phospholipid monolayer. Recent studies have revealed many new proteins, functions, and phenomena associated with LDs. In addition, a number of diseases related to LDs are beginning to be understood at the molecular level. It is now clear that LDs are not an inert store of excess lipids but are dynamically engaged in various cellular functions, some of which are not directly related to lipid metabolism. Compared to conventional membrane organelles, there are still many uncertainties concerning the molecular architecture of LDs and how each function is placed in a structural context. Recent findings and remaining questions are discussed.

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“…Accumulation of lipids occurs in many eukaryotic cells and is a rather common means of storing carbon and energy. Lipid droplets (LDs) can be found in all eukaryotes, such as yeast (Saccharomyces cerevisiae; Leber et al, 1994), mammals (Murphy, 2001;Hodges and Wu, 2010), Caenorhabditis elegans (Zhang et al, 2010;Mak, 2012), Drosophila melanogaster (Beller et al, 2006(Beller et al, , 2010, and plants (Hsieh and Huang, 2004), but also in prokaryotes (Wältermann et al, 2005). The basic structure of an LD is a core of neutral lipids covered by a phospholipid monolayer.…”

mentioning

confidence: 99%

Specialization of Oleosins in Oil Body Dynamics during Seed Development in Arabidopsis Seeds

et al. 2014

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Oil bodies (OBs) are seed-specific lipid storage organelles that allow the accumulation of neutral lipids that sustain plantlet development after the onset of germination. OBs are covered with specific proteins embedded in a single layer of phospholipids. Using fluorescent dyes and confocal microscopy, we monitored the dynamics of OBs in living Arabidopsis (Arabidopsis thaliana) embryos at different stages of development. Analyses were carried out with different genotypes: the wild type and three mutants affected in the accumulation of various oleosins (OLE1, OLE2, and OLE4), three major OB proteins. Image acquisition was followed by a detailed statistical analysis of OB size and distribution during seed development in the four dimensions (x, y, z, and t). Our results indicate that OB size increases sharply during seed maturation, in part by OB fusion, and then decreases until the end of the maturation process. In single, double, and triple mutant backgrounds, the size and spatial distribution of OBs are modified, affecting in turn the total lipid content, which suggests that the oleosins studied have specific functions in the dynamics of lipid accumulation.The seed is a complex, specific structure that allows a quiescent plant embryo to cope with unfavorable germinating conditions and also permits dissemination of the species. To achieve these functions, seeds accumulate reserve compounds that will ensure the survival of the embryo and fuel the growth of the plantlet upon germination. Accumulation of lipids occurs in many eukaryotic cells and is a rather common means of storing carbon and energy. Lipid droplets (LDs) can be found in all eukaryotes, such as yeast (Saccharomyces cerevisiae;

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Proteomic insights into an expanded cellular role for cytoplasmic lipid droplets

Cited by 142 publications

References 92 publications

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Not Just Fat: The Structure and Function of the Lipid Droplet

Specialization of Oleosins in Oil Body Dynamics during Seed Development in Arabidopsis Seeds

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