NEB UK - New England Biolabs (UK)
NEB UK - New England Biolabs (UK)
NEB UK - New England Biolabs (UK)
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Cell Signaling Technology <strong>New</strong>s<br />
10<br />
Autophagy<br />
Autophagy is a catabolic process that results in the autophagosomic-lysosomal<br />
degradation of bulk cytoplasmic contents.<br />
Autophagy is generally activated by conditions of nutrient deprivation<br />
but has also been associated physiological processes<br />
such as development, differentiation, neurodegenerative diseases,<br />
infection and cancer. The kinase mTOR is a critical regulator<br />
of autophagy induction. Upon growth-factor mediated activation<br />
of PI3K/Akt and MAP kinase signaling, activated mTOR<br />
promotes cell growth and protein translation, and suppresses<br />
autophagy; mTOR is negatively regulated by AMPK and p53 signaling<br />
pathways, which promote autophagy.<br />
The molecular machinery responsible for autophagy was largely<br />
discovered in yeast and are referred to as autophagy-related<br />
(Atg) genes. Autophagy is induced by a class III PI3 kinase lipidkinase<br />
complex that includes the tumor suppressor Beclin -1 (Atg<br />
6) as an essential component. Two widely conserved ubiquitinlike<br />
conjugation systems, LC3 (Atg8)-phosphatdylethanolamine<br />
and Atg12-Atg5 function in autophagosomal vesicle formation.<br />
Autophagy and apoptosis are connected both positively and<br />
negatively. During nutrient deficiency, autophagy functions as<br />
a pro-survival mechanism; however, excessive autophagy leads<br />
to autophagic cell death, a process morphologically distinct<br />
from apoptosis. Despite this morphological difference, extensive<br />
cross-talk occurs between autophagy and apoptosis. Several proapoptotic<br />
signals, such as TNF, TRAIL and FADD, also induce autophagy<br />
and pro-survival signaling through the PI3K/Akt/mTOR<br />
pathway suppresses autophagy. Additionally, Bcl-2 binds Beclin-1<br />
to inhibit Beclin-1-dependent autophagy, thereby functioning<br />
both as a pro-survival and as an anti-autophagic regulator.<br />
Precursor LC3B (dark red) is cleaved by Atg4 (yellow), then further processed by Atg7 and Atg3 (not shown) to produce a lipidated form (bright red) that becomes<br />
associated with autophagosomal membranes (background). Free Atg12 (orange) is conjugated to Atg5 (brown) by a ubiquitin-like interaction; Atg12+5 then bind Atg16<br />
(yellow-brown). This complex is involved in formation of the autophagosome membrane, possibly acting as a scaffold for membrane extension.
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