Regulation of mammalian autophagy in physiology and pathophysiology.
(Macro)autophagy is a bulk degradation process that mediates the clearance of long-lived proteins and organelles. Autophagy is initiated by double-membraned structures, which engulf portions of cytoplasm. The resulting autophagosomes ultimately fuse with lysosomes, where their contents are degraded. Although the term autophagy was first used in 1963, the field has witnessed dramatic growth in the last 5 years, partly as a consequence of the discovery of key components of its cellular machinery. In this review we focus on mammalian autophagy, and we give an overview of the understanding of its machinery and the signaling cascades that regulate it. As recent studies have also shown that autophagy is critical in a range of normal human physiological processes, and defective autophagy is associated with diverse diseases, including neurodegeneration, lysosomal storage diseases, cancers, and Crohn's disease, we discuss the roles of autophagy in health and disease, while trying to critically evaluate if the coincidence between autophagy and these conditions is causal or an epiphenomenon. Finally, we consider the possibility of autophagy upregulation as a therapeutic approach for various conditions.
Ravikumar
Brinda
B
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Cambridge, United Kingdom.
Sarkar
Sovan
S
Davies
Janet E
JE
Futter
Marie
M
Garcia-Arencibia
Moises
M
Green-Thompson
Zeyn W
ZW
Jimenez-Sanchez
Maria
M
Korolchuk
Viktor I
VI
Lichtenberg
Maike
M
Luo
Shouqing
S
Massey
Dunecan C O
DC
Menzies
Fiona M
FM
Moreau
Kevin
K
Narayanan
Usha
U
Renna
Maurizio
M
Siddiqi
Farah H
FH
Underwood
Benjamin R
BR
Winslow
Ashley R
AR
Rubinsztein
David C
DC
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008322:Mammals / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological