J. Indian Inst. Sci. | VOL xxx:x | xxx–xxx 2017 | journal.iisc.ernet.in 1 3 Multifaceted Housekeeping Functions of Autophagy 1 Introduction Autophagy, an intracellular evolutionarily con- served process, involves engulfment of unwanted proteins and organelles by double-membrane vesicles, called autophagosomes, which then fuse with the lysosomes/vacuole, and the engulfed cargo is subsequently degraded. It is a cell sur- vival mechanism under stress conditions and it also play important roles in many other intra-cel- lular processes like protein and organelle turno- ver and transport of some of the vacuolar enzymes. This process can be divided into various steps, including autophagy induction, nucleation, autophagosome formation, maturation, fusion with the lysosomes/vacuole, degradation of the cargo, and recycling of the precursor molecules, such as amino acids, lipids, and nucleotides, back to the cytoplasm. Autophagy is a tightly regulated cellular mechanism and its flux varies depending on the cell type(s) of an organism. Autophagy is involved in various physiological roles, such as cellular homeostasis, embryonic development, antigen presentation, protein quality control, and maintenance of the amino-acid pool during star- vation conditions. It is also implicated in various pathophysiological diseases, such as infection, cancer, diabetes, and neurodegeneration. Autophagosomes: The “Pac- Man” like double membrane vesicles involved in macroau- tophagy. Sarika Chinchwadkar, Sreedevi Padmanabhan, Piyush Mishra, Sunaina Singh, S. N. Suresh, Somya Vats, Gaurav Barve, Veena Ammanathan and Ravi Manjithaya * J. Indian Inst. Sci. A Multidisciplinary Reviews Journal ISSN: 0970-4140 Coden-JIISAD Abstract | Autophagy is an evolutionarily conserved intracellular deg- radation process in which cytoplasmic components are captured in double membrane vesicles called autophagosomes and delivered to lys- osomes for degradation. This process has an indispensable role in main- taining cellular homeostasis. The rate at which the dynamic turnover of cellular components takes place via the process of autophagy is called autophagic flux. In this review, we discuss about the orchestrated events in the autophagy process, transcriptional regulation, role of autophagy in some major human diseases like cancer, neurodegeneration (aggre- phagy), and pathogenesis (xenophagy). In addition, autophagy has non- canonical roles in protein secretion, thus demonstrating the multifaceted role of autophagy in intracellular processes. REVIEW ARTICLE Although autophagy is predominantly a cytosolic event, the nucleus exerts a consider- able control in the extent of autophagy response, especially during adverse conditions, such as starvation. Depending on the cargo it captures, autophagy is broadly classified as general and selective autophagy. For example, as a response to nutrient deprivation, general autophagy is triggered where it captures random portion of cytosol. In contrast, selective autophagy ensures specific capture of cytosolic cargo, such as dam- aged or superfluous organelles. When selective autophagy captures and degrades mitochondria, the process is termed as mitophagy. Similarly, autophagic degradation of peroxisomes (pex- ophagy), Golgi (golgiphagy), ER (ER-phagy), ribosomes (ribophagy), etc., have been docu- mented. 1 The genes comprising the autophagy machinery are named as ATG (AuTophaGy related gene). 1 2 Process of Autophagy 2.1 Autophagy Induction The initial characterization of autophagy flux with respect to involvement of molecular play- ers was carried out in yeast extensively. Although recycling of the cytoplasmic contents happens at © Indian Institute of Science 2017. Autophagy Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560 064, India *ravim@jncasr.ac.in