The different roles of selective autophagic protein degradation in mammalian cells

Da-wei Wang, Zhen-ju Peng, Guang-fang Ren and Guang-xin Wang _

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Oncotarget. 2015; 6:37098-37116. https://doi.org/10.18632/oncotarget.5776

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Da-wei Wang1, Zhen-ju Peng2, Guang-fang Ren2 and Guang-xin Wang2

1 Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, China

2 Medical Institute of Paediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, China

Correspondence to:

Guang-xin Wang, email:

Keywords: autophagy, protein, degradation, modification, autophagy receptor

Received: July 03, 2015 Accepted: August 31, 2015 Published: September 22, 2015


Autophagy is an intracellular pathway for bulk protein degradation and the removal of damaged organelles by lysosomes. Autophagy was previously thought to be unselective; however, studies have increasingly confirmed that autophagy-mediated protein degradation is highly regulated. Abnormal autophagic protein degradation has been associated with multiple human diseases such as cancer, neurological disability and cardiovascular disease; therefore, further elucidation of protein degradation by autophagy may be beneficial for protein-based clinical therapies. Macroautophagy and chaperone-mediated autophagy (CMA) can both participate in selective protein degradation in mammalian cells, but the process is quite different in each case. Here, we summarize the various types of macroautophagy and CMA involved in determining protein degradation. For this summary, we divide the autophagic protein degradation pathways into four categories: the post-translational modification dependent and independent CMA pathways and the ubiquitin dependent and independent macroautophagy pathways, and describe how some non-canonical pathways and modifications such as phosphorylation, acetylation and arginylation can influence protein degradation by the autophagy lysosome system (ALS). Finally, we comment on why autophagy can serve as either diagnostics or therapeutic targets in different human diseases.

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