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Selective degradation of p62 by autophagy

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Abstract

The autophagy–lysosome pathway is a highly conserved bulk degradation system in eukaryotes. During starvation, cytoplasmic constituents are non-selectively degraded by autophagy, and the resulting amino acids are utilized for cell survival. By taking advantage of mouse genetics, many physiological functions of mammalian autophagy have been uncovered. Growing lines of evidences have revealed the essential role of constitutive (or basal) autophagy in cellular homeostasis through its selectivity. p62, one of the selective substrates for autophagy, plays a key role in the formation of cytoplasmic proteinaceous inclusion, a hallmark of conformational diseases such as Alzheimer’s disease, Parkinson’s disease, and various chronic liver disorders. In this review, we discuss the physiological roles of the selective turnover of p62 by autophagy and their molecular mechanisms.

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Abbreviations

Ape1:

Aminopeptidase I

Atg:

Autophagy-related

DISC:

Death-inducing signaling complex

LC3:

Microtubule-associated protein 1 light chain 3

LIR:

LC3-interacting region

LRS:

LC3 recognition sequence

PB1:

Phox and Bem1p

PE:

Phosphatidylethanolamine

UBA:

Ubiquitin-associated domain

UPS:

Ubiquitin–proteasome system

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Acknowledgments

This work is supported by Grants-in-Aid for Science Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (M.K.) and from the Japan Science and Technology Agency and the Ministry of Education, Science and Culture of Japan (M.K.).

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Authors and Affiliations

  1. Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, 156-8506, Japan

    Yoshinobu Ichimura & Masaaki Komatsu

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  1. Yoshinobu Ichimura
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  2. Masaaki Komatsu
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Correspondence to Masaaki Komatsu.

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Ichimura, Y., Komatsu, M. Selective degradation of p62 by autophagy. Semin Immunopathol 32, 431–436 (2010). https://doi.org/10.1007/s00281-010-0220-1

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