Biol. Rev. (2019), pp. 000 – 000. 1 doi: 10.1111/brv.12515 Molecular interplay of autophagy and endocytosis in human health and diseases Kewal K. Mahapatra, Debasna P. Panigrahi, Prakash P. Praharaj, Chandra S. Bhol, Srimanta Patra, Soumya R. Mishra, Bishnu P. Behera and Sujit K. Bhutia ∗ Department of Life Science, National Institute of Technology Rourkela, Sundergarh, Odisha 769008, India ABSTRACT Autophagy, an evolutionarily conserved process for maintaining the physio-metabolic equilibrium of cells, shares many common effector proteins with endocytosis. For example, tethering proteins involved in fusion like Ras-like GTPases (Rabs), soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), lysosomal-associated membrane protein (LAMP), and endosomal sorting complex required for transport (ESCRT) have a dual role in endocytosis and autophagy, and the trafficking routes of these processes converge at lysosomes. These common effectors indicate an association between budding and fusion of membrane-bound vesicles that may have a substantial role in autophagic lysosome reformation, by sensing cellular stress levels. Therefore, autophagy–endocytosis crosstalk may be significant and implicates a novel endocytic regulatory pathway of autophagy. Moreover, endocytosis has a pivotal role in the intake of signalling molecules, which in turn activates cascades that can result in pathophysiological conditions. This review discusses the basic mechanisms of this crosstalk and its implications in order to identify potential novel therapeutic targets for various human diseases. Key words: autophagy, endocytosis, autophagosome, amphisome, lysosome. CONTENTS I. Introduction .............................................................................................. 2 II. Autophagy and its regulation ............................................................................. 2 III. Overview of the endocytic pathway ...................................................................... 4 IV. The interplay of conventional and non-conventional pathways in autophagy dynamics ................. 4 V. Convergence of autophagy and endocytosis .............................................................. 5 (1) Processes involved in autophagy and endocytosis ..................................................... 5 (a) Fusion of an autophagosome with a lysosome .................................................... 5 (b) Autophagic lysosome reformation ................................................................ 6 (2) Proteins involved in autophagy – endocytosis crosstalk ................................................ 7 (a) Rabs .............................................................................................. 8 (b) SNAREs .......................................................................................... 9 (c) LAMPs ........................................................................................... 10 (d ) ESCRTs .......................................................................................... 10 VI. Autophagy and endocytosis in human health and diseases ............................................... 11 VII. Conclusions .............................................................................................. 12 VIII. Acknowledgements ....................................................................................... 13 IX. References ................................................................................................ 13 * Address for correspondence (Tel: +91 0661 2462686; Fax +91661 2472926; E-mail: sujitb@nitrkl.ac.in; bhutiask@gmail.com) Biological Reviews (2019) 000 – 000  2019 Cambridge Philosophical Society