Microautophagy is one of the three common forms of autophagy, but unlike macroautophagy and chaperone-mediated autophagy, it is mediated—in mammals by lysosomal action or in plants and fungi by vacuolar action—by direct engulfment of the cytoplasmic cargo. Cytoplasmic material is trapped in the lysosome/vacuole by a random process of membrane invagination.
The microautophagic pathway is especially important for survival of cells under conditions of starvation, nitrogen deprivation, or after treatment with rapamycin. Generally a non-selective process, there are three special cases of a selective microautophagic pathway: micropexophagy, piecemeal microautophagy of the nucleus, and micromitophagy, all which are activated only under a specific conditions.
Functions of microautophagy
Microautophagy together with
macroautophagy is necessary for nutrient recycling under starvation. Microautophagy due to degradation of
lipids incorporated into vesicles regulates the composition of
lysosomal/
vacuolar membrane.
Microautophagic pathway functions also as one of the mechanism of
glycogen delivery into the
lysosomes.
This autophagic pathway engulfs multivesicular bodies formed after
endocytosis therefore it plays role in membrane proteins turnover.
Microautophagy is also connected with
organellar size maintenance, composition of biological membranes, cell survival under nitrogen restriction, and the transition pathway from starvation-induced growth arrest to logarithmic growth.
Non-selective microautophagy
Non-selective microautophagic process can be dissected into 5 distinct steps. The majority of experiments were done in
yeast (vacuolar invaginations) but the molecular principles seem to be more general.
Membrane invagination and autophagic tubes formation
Invagination is a constitutive process but its frequency is dramatically increased during periods of starvation. Invagination is a
Tubular gland process by which is formed the
autophagic tube.
Formation of the autophagic tubes is mediated through Atg7-dependent ubiquitin-like conjugation (Ublc) or via vacuolar transporter chaperone (VTC) molecular complex which acts through calmodulin-dependent manner. Calmodulin involvement in tube formation is calcium independent process.
Vesicle formation
The mechanism of vesicle formation is based on lateral sorting mechanism. Changed composition of
membrane molecules (
lipid enrichment in the autophagic tubes due to removal of transmembrane proteins) leads spontaneous vesicle formation via phase separation mechanism.
The process of microautophagic vesicle formation is similar to multivesicular bodies formation process
Vesicle expansion and scission
Enlargement of vesicle is mediated by binding
enzymes inside of unclosed vesicle. Basically, this process is reversal to
endocytosis. Process follows by pich of the vesicle into the lysosomal/vacuolar lumen. This process is independent on
SNARE proteins.
Vesicle degradation and recycling
Vesicle moves freely in the lumen and during the time is degraded by
hydrolases (ec. Atg15p). Nutrients are then released by Atg22p.
Selective microautophagy
Process of non-selective microautophagy can be observed in all types of
eukaryotic cells. On the other hand, selective microautophagy is commonly observed in
yeast cells.
Three types of selective microautophagy selective microautophagy can be distinguished: micropexophagy, piecemeal microautophagy of the nucleus and micromitophagy