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The role of mammalian autophagy in protein metabolism.

Mizushima N - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2007)

Bottom Line: Autophagy is usually suppressed at low levels but can be upregulated during periods of nutrient starvation, which facilitates cell survival.In addition to this fundamental role, basal autophagy was recently revealed to be important for constitutive turnover of intracellular proteins and organelles.This review will discuss the biological significance of autophagy, particularly focusing on its implications in protein metabolism in mammals.

View Article: PubMed Central - PubMed

Affiliation: SORST, Japan Science and Technology Corporation, Kawaguchi, Japan .

ABSTRACT
Autophagy is in principle a non-selective degradation system within cells, which is conserved in all eukaryotic cells. Autophagy is usually suppressed at low levels but can be upregulated during periods of nutrient starvation, which facilitates cell survival. In addition to this fundamental role, basal autophagy was recently revealed to be important for constitutive turnover of intracellular proteins and organelles. Autophagy has been considered to be involved also in presentation of endogenous antigens, degradation of invasive bacteria, tumor suppression, cell death and development. This review will discuss the biological significance of autophagy, particularly focusing on its implications in protein metabolism in mammals.

No MeSH data available.


Related in: MedlinePlus

Target to the lysosome via three types of autophagy.(1) macroautophagy: A portion of cytoplasm is enclosed by the autophagic isolation membrane, which eventually results in the formation of a double membrane structure, called autophagosome. The outer membrane of the autophagosome then fuses with the lysosome where the cytoplasm-derived materials are degraded.(2) microautophagy: A small portion of cytoplasm is engulfed by the lysosome membrane itself.(3) Chaperone-mediated autophagy (CMA): Cytosolic proteins containing KFERQ-like motifs are recognized by a cytosolic chaperone Hsc70 and co-chaperones. When the resulting complexes bind to a lysosomal receptor, Lamp2a, the substrates are unfolded and transported into the lysosomal lumen for degradation.
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f1-83_039: Target to the lysosome via three types of autophagy.(1) macroautophagy: A portion of cytoplasm is enclosed by the autophagic isolation membrane, which eventually results in the formation of a double membrane structure, called autophagosome. The outer membrane of the autophagosome then fuses with the lysosome where the cytoplasm-derived materials are degraded.(2) microautophagy: A small portion of cytoplasm is engulfed by the lysosome membrane itself.(3) Chaperone-mediated autophagy (CMA): Cytosolic proteins containing KFERQ-like motifs are recognized by a cytosolic chaperone Hsc70 and co-chaperones. When the resulting complexes bind to a lysosomal receptor, Lamp2a, the substrates are unfolded and transported into the lysosomal lumen for degradation.

Mentions: Intracellular protein degradation systems can be roughly classified into two groups: one that is selective and another that is non-selective. The selective degradation is primarily carried by the ubiquitin-proteasome system present in the cytoplasm and nucleus. On the other hand, the latter type occurs mainly in the lysosome that is an organelle specialized for degradation. The degradation and recycling of cytoplasmic content by lysosomes is generically referred to as autophagy.1)–4) Three distinct types of autophagy have been identified, macroautophagy, microautophagy and chaperone-mediated autophagy (CMA) (Fig. 1). CMA is mediated by chaperones that specifically recognize substrates. Thus, CMA is a type of selective, rather than a bulk or non-selective, degradation system.1) Microautophagy has been proposed to occur based on morphological change of lysosome, but its molecular mechanism remains unknown. Among these, the molecular mechanism and physiologic significance of macroautophagy have been best studied. Therefore, under most circumstances, autophagy refers to macroautophagy. Upon induction of autophagy, a membrane sac called the isolation membrane elongates and encloses a portion of cytoplasm. Complete sequestration, which takes about 10 minutes, results in formation of a double membrane structure called the autophagosome. The diameter is usually 0.5–1.5 μm in mammalian cells and 0.3–0.9 μm in yeast cells. Organelles such as mitochondria and ER fragments are often enclosed. When the outer membrane of autophagosome fuses with the lysosome, the inner membrane of the autophagosome and the cytoplasm-derived materials are degraded by lysosomal hydrolases.


The role of mammalian autophagy in protein metabolism.

Mizushima N - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2007)

Target to the lysosome via three types of autophagy.(1) macroautophagy: A portion of cytoplasm is enclosed by the autophagic isolation membrane, which eventually results in the formation of a double membrane structure, called autophagosome. The outer membrane of the autophagosome then fuses with the lysosome where the cytoplasm-derived materials are degraded.(2) microautophagy: A small portion of cytoplasm is engulfed by the lysosome membrane itself.(3) Chaperone-mediated autophagy (CMA): Cytosolic proteins containing KFERQ-like motifs are recognized by a cytosolic chaperone Hsc70 and co-chaperones. When the resulting complexes bind to a lysosomal receptor, Lamp2a, the substrates are unfolded and transported into the lysosomal lumen for degradation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756738&req=5

f1-83_039: Target to the lysosome via three types of autophagy.(1) macroautophagy: A portion of cytoplasm is enclosed by the autophagic isolation membrane, which eventually results in the formation of a double membrane structure, called autophagosome. The outer membrane of the autophagosome then fuses with the lysosome where the cytoplasm-derived materials are degraded.(2) microautophagy: A small portion of cytoplasm is engulfed by the lysosome membrane itself.(3) Chaperone-mediated autophagy (CMA): Cytosolic proteins containing KFERQ-like motifs are recognized by a cytosolic chaperone Hsc70 and co-chaperones. When the resulting complexes bind to a lysosomal receptor, Lamp2a, the substrates are unfolded and transported into the lysosomal lumen for degradation.
Mentions: Intracellular protein degradation systems can be roughly classified into two groups: one that is selective and another that is non-selective. The selective degradation is primarily carried by the ubiquitin-proteasome system present in the cytoplasm and nucleus. On the other hand, the latter type occurs mainly in the lysosome that is an organelle specialized for degradation. The degradation and recycling of cytoplasmic content by lysosomes is generically referred to as autophagy.1)–4) Three distinct types of autophagy have been identified, macroautophagy, microautophagy and chaperone-mediated autophagy (CMA) (Fig. 1). CMA is mediated by chaperones that specifically recognize substrates. Thus, CMA is a type of selective, rather than a bulk or non-selective, degradation system.1) Microautophagy has been proposed to occur based on morphological change of lysosome, but its molecular mechanism remains unknown. Among these, the molecular mechanism and physiologic significance of macroautophagy have been best studied. Therefore, under most circumstances, autophagy refers to macroautophagy. Upon induction of autophagy, a membrane sac called the isolation membrane elongates and encloses a portion of cytoplasm. Complete sequestration, which takes about 10 minutes, results in formation of a double membrane structure called the autophagosome. The diameter is usually 0.5–1.5 μm in mammalian cells and 0.3–0.9 μm in yeast cells. Organelles such as mitochondria and ER fragments are often enclosed. When the outer membrane of autophagosome fuses with the lysosome, the inner membrane of the autophagosome and the cytoplasm-derived materials are degraded by lysosomal hydrolases.

Bottom Line: Autophagy is usually suppressed at low levels but can be upregulated during periods of nutrient starvation, which facilitates cell survival.In addition to this fundamental role, basal autophagy was recently revealed to be important for constitutive turnover of intracellular proteins and organelles.This review will discuss the biological significance of autophagy, particularly focusing on its implications in protein metabolism in mammals.

View Article: PubMed Central - PubMed

Affiliation: SORST, Japan Science and Technology Corporation, Kawaguchi, Japan .

ABSTRACT
Autophagy is in principle a non-selective degradation system within cells, which is conserved in all eukaryotic cells. Autophagy is usually suppressed at low levels but can be upregulated during periods of nutrient starvation, which facilitates cell survival. In addition to this fundamental role, basal autophagy was recently revealed to be important for constitutive turnover of intracellular proteins and organelles. Autophagy has been considered to be involved also in presentation of endogenous antigens, degradation of invasive bacteria, tumor suppression, cell death and development. This review will discuss the biological significance of autophagy, particularly focusing on its implications in protein metabolism in mammals.

No MeSH data available.


Related in: MedlinePlus