Mapping Autophagy on to Your Metabolic Radar
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York; the Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York; and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York
- Corresponding author: Rajat Singh, .
Autophagy, which literally translates into “eating one's own self,” is an evolutionarily conserved cellular recycling program that maintains “in-house” quality control by turning over cytoplasmic components within lysosomes (1). Although the discovery of lysosomes dates back to the 1950s through the electron microscopic work of Christian De Duve, recent years have seen a growing interest in autophagy research, and reports now link compromised autophagy to a wide array of common human pathologies, for instance, neurodegenerative disorders, metabolic alterations, microbial pathogenesis, and cancers, to mention just a few (2). These studies support the idea that the “housekeeping” role of autophagy, in fact, translates to key physiological functions. For instance, recycling of oxidized proteins and aged organelles through autophagic degradation protects against cellular toxicity and death (3). Recent findings now highlight roles for autophagy in mobilization of diverse cellular energy stores (4) and in adipocyte differentiation (5,6), thus presenting autophagy as an emerging player in the metabolic arena. As novel functions for autophagy continue to unfold, it becomes critical to be able to precisely monitor autophagy in diverse physiological systems. This article comments on the fundamental developments on roles for autophagy in metabolic regulation and discusses currently available methods to monitor autophagy.
AUTOPHAGY: THE MACHINERY AND REGULATORY ELEMENTS
Mammalian cells exhibit three distinct forms of autophagy to deliver cytosolic cargo to the lysosomes, namely, macroautophagy, chaperone-mediated autophagy, and microautophagy (1). Traditionally, autophagy was considered a one-lane system for protein turnover and a mechanism for replenishing the intracellular amino acid pool during starvation. However, it is now becoming increasingly clear that autophagy, in particular macroautophagy, exhibits significant versatility in its ability to degrade mitochondria (mitophagy), endoplasmic reticulum (reticulophagy), ribosomes (ribophagy), and peroxisomes (pexophagy) (1). The second form of autophagy, chaperone-mediated autophagy, displays functional selectivity for the lysosomal targeting of specific soluble cytosolic proteins with the KFERQ signature …