How to control self-digestion: transcriptional, post-transcriptional, and post-translational regulation of autophagy

Abstract

Macroautophagy (hereafter autophagy), literally defined as a type of self-eating, is a dynamic cellular process in which cytoplasm is sequestered within a unique compartment termed the phagophore. Upon completion, the phagophore matures into a double-membrane autophagosome that fuses with the lysosome or vacuole, allowing degradation of the cargo. Nonselective autophagy is primarily a cytoprotective response to various types of stress; however, the process can also be highly selective. Autophagy is involved in various aspects of cell physiology, and its dysregulation is associated with a range of diseases. The regulation of autophagy is complex, and the process must be properly modulated to maintain cellular homeostasis. In this review, we focus on the current state of knowledge concerning transcriptional, post-transcriptional, and post-translational regulation of autophagy in yeast and mammals.

Keywords: lysosome; phagophore; stress; vacuole; yeast.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Figures

Figure 1

The morphology of autophagy in yeast and mammals. The primary membrane structures involved in autophagy are depicted. The phagophore is the initial sequestering compartment that expands into the double-membrane autophagosome. The latter fuses with the vacuole (yeast) or the lysosome (mammals) to allow access to, and degradation of, the cargo (the image depicts the sequestration of random cytoplasm including an organelle). The resulting breakdown products are subsequently released back into the cytosol through integral membrane permeases for reuse.

Figure 2

The regulation of autophagy in mammalian cells through FOXO (forkhead box O) proteins. FOXO1 and FOXO3 shuttle between the cytosol and nucleus, controlling autophagy through transcriptional regulation, and by directly binding to ATG7 (autophagy related 7).

Figure 3

Coordinated regulation of ULK1 (unc-51 like autophagy activating kinase 1) by AMPK (AMP-activated protein kinase) and MTOR (mechanistic target of rapamycin). Phosphorylation-dependent regulation of ULK1 by AMPK and MTOR plays crucial roles in modulating autophagy activity. Arrows and bars indicate stimulation and inhibition, respectively. Green or red arrows and bars (or proteins) indicate events (or components) that promote or inhibit autophagy, respectively. Modified from Figure 8 of [58].