Direct targeting of proteins to lipid droplets demonstrated by time-lapse live cell imaging

Tanaka, Torahiko; Kuroda, Kensuke; Ikeda, Masanori; Kato, Naoya; Shimizu, Kazufumi; Makishima, Makoto

doi:10.1016/j.jbiosc.2013.05.006

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…One of these is NS4B, which contains both ER and lipid droplet targeting signals. Surprisingly, in the absence of the ER hydrophobic signal, the protein appears to go directly to droplets from the cytosol, as determined by fluorescence microscopy (Tanaka et al, 2013 ).…”

Section: Relationship With the Ermentioning

confidence: 99%

The lipid droplet—a well-connected organelle

Gao

Goodman

2015

Front. Cell Dev. Biol.

202

177

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Our knowledge of inter-organellar communication has grown exponentially in recent years. This review focuses on the interactions that cytoplasmic lipid droplets have with other organelles. Twenty-five years ago droplets were considered simply particles of coalesced fat. Ten years ago there were hints from proteomics studies that droplets might interact with other structures to share lipids and proteins. Now it is clear that the droplets interact with many if not most cellular structures to maintain cellular homeostasis and to buffer against insults such as starvation. The evidence for this statement, as well as probes to understand the nature and results of droplet interactions, are presented.

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Section: Relationship With the Ermentioning

confidence: 99%

The lipid droplet—a well-connected organelle

Gao

Goodman

2015

Front. Cell Dev. Biol.

202

177

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Section: Er To Droplet Traffickingmentioning

confidence: 94%

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

2017

Frontiers Research Topics

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“…mKeima was fused with the LD protein perilipin1 to localize mKeima to LDs. Lipophagy was clearly induced in constructs fusing the eLIR with perilipin1, but little with LDTS from hepatitis C virus 31 or PNPLA5 (Supplementary Fig. 2a) 32 .…”

Section: Development Of An Optimized Lipophagy Adaptor Proteinmentioning

confidence: 99%

Liver lipophagy ameliorates nonalcoholic steatohepatitis through lysosomal lipid exocytosis

Minami

Hoshino

Higuchi

et al. 2022

Preprint

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Nonalcoholic steatohepatitis (NASH) is a progressive disorder with aberrant lipid accumulation and subsequent inflammatory and profibrotic response. Therapeutic efforts at lipid reduction via increasing cytoplasmic lipolysis unfortunately worsens hepatitis due to toxicity of liberated fatty acid. An alternative approach could be lipid reduction through autophagic disposal, i.e., lipophagy. We engineered a synthetic adaptor protein to induce lipophagy, combining a lipid droplet-targeting signal with optimized LC3-interacting domain. Activating hepatocyte lipophagy in vivo strongly mitigated both steatosis and hepatitis in a diet-induced mouse NASH model. Mechanistically, activated lipophagy promoted the excretion of lipid from hepatocytes via lysosomal exocytosis, thereby suppressing harmful intracellular accumulation of nonesterified fatty acid. A high-content compound screen identified alpelisib and digoxin, clinically-approved compounds, as effective activators of lipophagy. Administration of alpelisib or digoxin in vivo strongly inhibited the transition to steatohepatitis. These data thus identify lipophagy as a promising therapeutic approach to prevent NASH progression.

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Direct targeting of proteins to lipid droplets demonstrated by time-lapse live cell imaging

Cited by 4 publications

References 12 publications

The lipid droplet—a well-connected organelle

The lipid droplet—a well-connected organelle

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

Liver lipophagy ameliorates nonalcoholic steatohepatitis through lysosomal lipid exocytosis

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