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From autophagy to mitophagy: the roles of P62 in neurodegenerative diseases

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Abstract

P62, also called sequestosome1 (SQSTM1), is the selective cargo receptor for autophagy to degenerate misfolded proteins. It has also been found to assist and connect parkin in pink1/parkin mitophagy pathway. Previous studies showed that p62 was in association with neurodegenerative diseases, and one of the diseases pathogenesis is P62 induced autophagy and mitophagy dysfunction. Autophagy is an important process to eliminate misfolded proteins. Intracellular aggregation including α-synuclein, Huntingtin, tau protein and ß-amyloid (Aß) protein are the misfolded proteins found in PD, HD and AD, respectively. P62 induced autophagy failure significantly accelerates misfolded protein aggregation. Mitophagy is the special autophagy, functions as the selective scavenger towards the impaired mitochondria. Mitochondrial dysfunction was confirmed greatly contribute to the occurrence of neurodegenerative diseases. Through assistance and connection with parkin, P62 is vital for regulating mitophagy, thus, aberrant P62 could influence the balance of mitophagy, and further disturb mitochondrial quality control. Therefore, accumulation of misfolded proteins leads to the aberrant P62 expression, aberrant P62 influence the balance of mitophagy, forming a vicious circle afterwards. In this review, we summarize the observations on the function of P62 relevant to autophagy and mitophagy in neurodegenerative diseases, hoping to give some clear and objective opinions to further study.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81371498 and 81771476 to WW).

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  1. Haiying Liu and Chunqiu Dai contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, No. 169 Changle West Road, Xi’an, 710032, People’s Republic of China

    Haiying Liu, Yunlong Fan, Baolin Guo & Wenting Wang

  2. Cadet Brigade, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Haiying Liu, Chunqiu Dai & Yunlong Fan

  3. College of Life Sciences & Research Center for Resource Peptide Drugs, Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources, Yan’an University, Yan’an, 716000, People’s Republic of China

    Keke Ren

  4. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, People’s Republic of China

    Tangna Sun

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  1. Haiying Liu
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Correspondence to Wenting Wang.

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Liu, H., Dai, C., Fan, Y. et al. From autophagy to mitophagy: the roles of P62 in neurodegenerative diseases. J Bioenerg Biomembr 49, 413–422 (2017). https://doi.org/10.1007/s10863-017-9727-7

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