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Lipases in lysosomes, what for?

Czaja MJ, Cuervo AM - Autophagy (2009)

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. czaja@aecom.yu.edu

ABSTRACT

We have all learned in textbooks that “lysosomes contain hydrolases able to degrade all types of intracellular molecules which include proteases, glycosidases, nucleotidases and lipases.” To date, the only logical explanation for the presence of lipases inside of lysosomes was for the degradation of lipoproteins internalized by endocytosis, and for the breakdown of intralysosomal vesicles derived from fusion with autophagosomes or multivesicular bodies. However, in our recent work we found a novel role for ysosomal lipases in the basic cellular process that regulates intracellular lipid stores that we have named “macrolipophagy”.

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Figure 1. Schematic model of macrolipophagy. Lipid droplet contents are continuously delivered to lysosomes for breakdown by macrolipophagy, a specialized form of autophagy. Our findings support the concept that portions of the lipid droplets are sequestered by in situ-formed limiting membranes of autophagic nature (enriched in LC3) that then seal to form autophagosomes. Microtubule-dependent fusion of these lipid droplet-containing autophagosomes with lysosomes leads to hydrolysis of triglycerides into free fatty acids that can be used by mitochondria to generate energy for the cells. FFA: free fatty acids; LC3: light chain type 3 protein.
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Figure 1: Figure 1. Schematic model of macrolipophagy. Lipid droplet contents are continuously delivered to lysosomes for breakdown by macrolipophagy, a specialized form of autophagy. Our findings support the concept that portions of the lipid droplets are sequestered by in situ-formed limiting membranes of autophagic nature (enriched in LC3) that then seal to form autophagosomes. Microtubule-dependent fusion of these lipid droplet-containing autophagosomes with lysosomes leads to hydrolysis of triglycerides into free fatty acids that can be used by mitochondria to generate energy for the cells. FFA: free fatty acids; LC3: light chain type 3 protein.

Mentions: Contrary to our preconceived idea that the limiting membrane of the autophagosome sequestered whole lipid droplets and delivered them to lysosomes for hydrolysis, we found that in most instances only a portion of the lipid droplet was engulfed at one time. In fact, conjugation of LC3 to form the limiting membrane occurred on the lipid droplet surface, resulting in a penetrating membrane that seals on itself, sequestering both lipids and lipid droplet structural proteins (Fig. 1). As with conventional macroautophagy, basal macrolipophagy does not seem to be a selective process, because portions of lipid droplets are engulfed along with other cytosolic cargo giving rise to autophagic vacuoles with heterogeneous content. However, as starvation persists, macroautophagy becomes somewhat selective as autophagosomes with only lipid droplet content in their lumens constitute the most abundant type of autophagic vacuole under this condition.


Lipases in lysosomes, what for?

Czaja MJ, Cuervo AM - Autophagy (2009)

Figure 1. Schematic model of macrolipophagy. Lipid droplet contents are continuously delivered to lysosomes for breakdown by macrolipophagy, a specialized form of autophagy. Our findings support the concept that portions of the lipid droplets are sequestered by in situ-formed limiting membranes of autophagic nature (enriched in LC3) that then seal to form autophagosomes. Microtubule-dependent fusion of these lipid droplet-containing autophagosomes with lysosomes leads to hydrolysis of triglycerides into free fatty acids that can be used by mitochondria to generate energy for the cells. FFA: free fatty acids; LC3: light chain type 3 protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643983&req=5

Figure 1: Figure 1. Schematic model of macrolipophagy. Lipid droplet contents are continuously delivered to lysosomes for breakdown by macrolipophagy, a specialized form of autophagy. Our findings support the concept that portions of the lipid droplets are sequestered by in situ-formed limiting membranes of autophagic nature (enriched in LC3) that then seal to form autophagosomes. Microtubule-dependent fusion of these lipid droplet-containing autophagosomes with lysosomes leads to hydrolysis of triglycerides into free fatty acids that can be used by mitochondria to generate energy for the cells. FFA: free fatty acids; LC3: light chain type 3 protein.
Mentions: Contrary to our preconceived idea that the limiting membrane of the autophagosome sequestered whole lipid droplets and delivered them to lysosomes for hydrolysis, we found that in most instances only a portion of the lipid droplet was engulfed at one time. In fact, conjugation of LC3 to form the limiting membrane occurred on the lipid droplet surface, resulting in a penetrating membrane that seals on itself, sequestering both lipids and lipid droplet structural proteins (Fig. 1). As with conventional macroautophagy, basal macrolipophagy does not seem to be a selective process, because portions of lipid droplets are engulfed along with other cytosolic cargo giving rise to autophagic vacuoles with heterogeneous content. However, as starvation persists, macroautophagy becomes somewhat selective as autophagosomes with only lipid droplet content in their lumens constitute the most abundant type of autophagic vacuole under this condition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. czaja@aecom.yu.edu

ABSTRACT

We have all learned in textbooks that “lysosomes contain hydrolases able to degrade all types of intracellular molecules which include proteases, glycosidases, nucleotidases and lipases.” To date, the only logical explanation for the presence of lipases inside of lysosomes was for the degradation of lipoproteins internalized by endocytosis, and for the breakdown of intralysosomal vesicles derived from fusion with autophagosomes or multivesicular bodies. However, in our recent work we found a novel role for ysosomal lipases in the basic cellular process that regulates intracellular lipid stores that we have named “macrolipophagy”.

Show MeSH
Related in: MedlinePlus