Autophagy in Disease - Protein Misfolding and Cellular Stress in Disease and Aging - page 79

Fig. 2. A simplified model of signalling pathways and major players that regulate macroautophagy. See text for more
details. AMP adenosine monophosphate, ATP adenosine-5 ′ -triphosphate, (m)TOR (mammalian) target of rapamycin, ROS
reactive oxygen species.

(ATP), reactive oxygen species (ROS), calcium, ceramide) either
directly or indirectly inhibit or stimulate autophagy through
TOR. The cell surface transporters that facilitate amino acid entry
into cells for activation of autophagy remain poorly characterised.
A simplified model of the signalling which regulates macroau-
tophagy is presented in Fig. 2 . Even though a complete and fully
integrated picture of autophagy regulation is not currently
available, some aspects have been covered in focussed reviews
( 21, 24, 25 ).

During microautophagy, the lysosomal membrane invaginates so as
to sequester and internalise cytosolic components in single mem-
brane vesicles (derived from the lysosomal membrane). These vesi-
cles are then degraded in the lysosomal lumen ( 14 ). In mammalian
cells, microautophagy seems to be unresponsive to classical mac-
roautophagic stimuli and the dissection of the mechanism, together
with the identification of proteins involved is still in its infancy.
Relatively little is known about the regulation of microautophagy.
Indeed, it is rarely considered by investigators when reporting on
autophagy. Microautophagic processes are better described in yeast
where some components of the characterised macroautophagic
machinery have been implicated in the selective microautophagy of
peroxisomes ( 26 ), the nucleus ( 27 ), and mitochondria ( 28 ). In
yeast, in addition to TOR, complexes involved in the regulation of

2.1.2. Microautophagy