Aberrant regulation of autophagy in mammalian diseases

Abstract

Autophagy is a major cellular metabolic pathway that facilitates degradation of a subset of long-lived proteins and cytoplasmic organelles in eukaryotic cells. This pathway plays a vital role in preserving the cellular homeostasis of the cells themselves, in addition to maintaining the normal physiological state of cell renewal. Many stressors, such as starvation, ischaemia and oxidative stress can induce autophagy. In addition to its physiological roles, autophagy also occurs in a wide variety of pathological processes, including tumour progression, metabolic disorders, and neurodegenerative and lung diseases. In recent years, a growing body of evidence has shown that autophagy also plays a key role in the development of mammalian diseases, a function that has garnered substantial attention and study. An in-depth understanding of the molecular role that autophagy plays in pathological settings is vital for both the diagnosis and treatment of mammalian diseases and will aid in the search for novel targets for therapeutic drug intervention. Here, we provide an integrated review of recent studies implicating autophagy dysfunction in the progression of mammalian disorders and summarize research suggesting that the molecular pathways involved in autophagy could serve as potential therapeutic targets.

Keywords: autophagy; heart disease; immune and inflammation; neurodegenerative disease.

Figure 1.

Stages of macroautophagy. During the nucleation phase, an isolation membrane, also known as a phagophore, engulfs protein aggregates and damaged organelles. The isolation membrane then extends, and the phagocytic membrane elongates to form a bilayer vesicle, referred to as an autophagosome. Autophagosomes fuse with lysosomes to form autolysosomes, which degrade the vesicular contents. After degradation, free amino acids, nucleotides, fatty acids and other components are released into the cytoplasm and recycled. (Online version in colour.)