Microautophagy: lesser-known self-eating

Abstract

Microautophagy, the non-selective lysosomal degradative process, involves direct engulfment of cytoplasmic cargo at a boundary membrane by autophagic tubes, which mediate both invagination and vesicle scission into the lumen. With its constitutive characteristics, microautophagy of soluble substrates can be induced by nitrogen starvation or rapamycin via regulatory signaling complex pathways. The maintenance of organellar size, membrane homeostasis, and cell survival under nitrogen restriction are the main functions of microautophagy. In addition, microautophagy is coordinated with and complements macroautophagy, chaperone-mediated autophagy, and other self-eating pathways. Three forms of selective microautophagy, including micropexophagy, piecemeal microautophagy of the nucleus, and micromitophagy, share common ground with microautophagy to some degree. As the accumulation of experimental data, the precise mechanisms that govern microautophagy are becoming more appreciated. Here, we review the microautophagic molecular machinery, its physiological functions, and relevance to human diseases, especially in diseases involving multivesicular bodies and multivesicular lysosomes.

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Abbreviations

Alp:

Alkaline phosphatase

Apg/Atg/ATG/Aut :

Autophagy-related gene

CMA:

Chaperone-mediated autophagy

Cpy:

Carboxypeptidase Y

CVT:

Cytoplasm-to-vacuole targeting

EGO:

Exit from rapamycin-induced growth arrest

ESCRT:

Endosomal sorting complex required for transport

hsc70:

Heat shock cognate 70

MIPA:

Micropexophagic membrane apparatus

MPT:

Mitochondrial permeability transition

MVB:

Multivesicular body

NV:

Nucleus–vacuole

PAS:

Pre-autophagosomal structure

PCD:

Programmed cell death

PE:

Phosphatidylethanolamine

PMN:

Piecemeal microautophagy of the nucleus

PVS:

Peri-vacuolar dot-like structures

ROS:

Reactive oxygen species

SNARE:

Soluble NSF attachment protein receptors

TOR:

Target of rapamycin

Ublc:

Ubiquitin-like conjugation

VSM:

Vacuolar sequestering membrane

VTC:

Vacuolar transporter chaperone

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Acknowledgments

We thank Dr. Bo Liu for providing constructive suggestions, Yi Wang, Zi-yue Li, Jun-jie Liu and Qian Liu for critically reading the manuscript, and Chi Yang, Hao-yu Hu for technical assistance. This work was supported in part by grants from the National Natural Science Foundation of China (No. 30970643, No. 81173093 and No. J1103518), and National Key Technologies R&D Program of 11th 5-year plan.

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Correspondence to Jin-ku Bao.

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Li, W., Li, J. & Bao, J. Microautophagy: lesser-known self-eating. Cell. Mol. Life Sci. 69, 1125–1136 (2012). https://doi.org/10.1007/s00018-011-0865-5

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Keywords

  • Autophagy
  • Microautophagy
  • Autophagic tube
  • Selective autophagy
  • Lysosomophagy