Theranostics 2021; 11(1):222-256. doi:10.7150/thno.49860

Review

Selective autophagy of intracellular organelles: recent research advances

Wen Li1,2,3#, Pengcheng He4,5#, Yuge Huang3#, Yi-Fang Li2, Jiahong Lu6, Min Li7, Hiroshi Kurihara2, Zhuo Luo2, Tian Meng1,8, Mashun Onishi9, Changle Ma10, Lei Jiang5, Yongquan Hu1,8, Qing Gong11, Dongxing Zhu12, Yiming Xu13, Rong Liu14,15, Lei Liu16, Cong Yi17, Yushan Zhu18, Ningfang Ma1,8, Koji Okamoto9, Zhiping Xie19, Jinbao Liu1✉, Rong-Rong He2✉, Du Feng1,8✉

1. Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
2. International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou 510632, China.
3. Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
4. Department of Cardiology, Guangdong General Hospital's Nanhai Hospital, Foshan, China.
5. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
6. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
7. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China.
8. Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, China.
9. Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
10. Shandong Provincial Key Laboratory of Plant Stress, College of Life Sciences, Shandong Normal University, Wenhua East Road 88, Jinan 250014, China.
11. Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China.
12. Guangzhou Institute of Cardiovascular Diseases, The Second Affiliated Hospital, Key Laboratory of Cardiovascular Diseases, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
13. School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China.
14. Department of Food Science, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
15. National Center for International Research on Animal Gut Nutrition, Nanjing, Jiangsu 210095, China.
16. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences; Beijing, China.
17. Department of Biochemistry, and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
18. State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
19. State Key Laboratory of Microbial Metabolism & Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
#These authors contributed equally to this work.

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Citation:
Li W, He P, Huang Y, Li YF, Lu J, Li M, Kurihara H, Luo Z, Meng T, Onishi M, Ma C, Jiang L, Hu Y, Gong Q, Zhu D, Xu Y, Liu R, Liu L, Yi C, Zhu Y, Ma N, Okamoto K, Xie Z, Liu J, He RR, Feng D. Selective autophagy of intracellular organelles: recent research advances. Theranostics 2021; 11(1):222-256. doi:10.7150/thno.49860. Available from http://www.thno.org/v11p0222.htm

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Abstract

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, etc. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, etc. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.

Keywords: selective autophagy, autophagy receptor, mitophagy, ER-phagy, proteaphagy, ribophagy, pexophagy, lipophagy, lysophagy, nucleophagy