A systems biology viewpoint on autophagy in health and disease.
OBJECTIVE
The field of autophagy is rapidly expanding to encompass many important areas of cell biology, physiology and disease. Recent discoveries and tools allow the connection of the autophagy pathway to other cellular signals and processes, thus beginning a systematic approach to elucidation of autophagy components, functions and connections.


RESULTS
We outline recent discoveries illustrating the role of autophagy in Parkinson's disease, inflammatory bowel disease (IBD) and cancer. Recently important details of the mechanisms by which autophagy operates in these contexts have been elucidated. We illustrate how autophagy can be triggered by diverse stimuli and how cell fate is determined by the responses to many signals and stresses. We discuss the known links between autophagy and apoptosis and present a working model of the current interactions between autophagy components, apoptosis and cell cycle control at different stages of autophagic vesicle progression.


CONCLUSIONS
Autophagy represents not only an essential metabolic process, but a hub which responds to diverse stresses and signals to aid cell survival or control cell fate. There are currently many known links between autophagy and disease states, and the pace of discovery appears to be accelerating. Thus an understanding of autophagy is likely to be crucial to current and future approaches to therapy. Here we give a systems biology view of the autophagy field and how it is being connected to other pathways, such as apoptosis and responses to reactive oxygen damage.
Huett
Alan
A
Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ahuett@ccib.mgh.harvard.edu
Goel
Gautam
G
Xavier
Ramnik J
RJ
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology*; D008107:Liver Diseases / Q000503:physiopathology*; D009369:Neoplasms / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D049490:Systems Biology
D017382:Reactive Oxygen Species