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Microautophagy is one of the three common forms of autophagic pathway, but unlike
macroautophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
and
chaperone-mediated autophagy Chaperone-mediated autophagy (CMA) refers to the chaperone-dependent selection of soluble cytosolic proteins that are then targeted to lysosomes and directly translocated across the lysosome membrane for degradation. The unique features of this type ...
, it is mediated—in
mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
by
lysosomal A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...
action or in
plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...
and
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
by
vacuolar A vacuole () is a membrane-bound organelle which is present in Plant cell, plant and Fungus, fungal Cell (biology), cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water ...
action—by direct engulfment of the
cytoplasmic In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. Th ...
cargo. Cytoplasmic material is trapped in the lysosome/vacuole by a random process of
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
invagination. The microautophagic pathway is especially important for survival of
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
under conditions of starvation,
nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
deprivation, or after treatment with
rapamycin Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, ...
. 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 Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
is necessary for nutrient recycling under starvation. Microautophagy due to degradation of
lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
incorporated into
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
regulates the composition of
lysosomal A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...
/
vacuolar A vacuole () is a membrane-bound organelle which is present in Plant cell, plant and Fungus, fungal Cell (biology), cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water ...
membrane. Microautophagic pathway functions also as one of the mechanism of
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...
delivery into the
lysosomes A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prote ...
. This autophagic pathway engulfs
multivesicular bodies Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can f ...
formed after
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
therefore it plays role in
membrane proteins Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...
turnover. Microautophagy is also connected with
organellar In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
size maintenance, composition of
biological membranes A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ce ...
, 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. Majority of experiments were done on
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
(vacuolar invaginations) but the molecular principles seem to be more general


Membrane invagination and autophagic tubes formation

Invagination Invagination is the process of a surface folding in on itself to form a cavity, pouch or tube. In developmental biology, invagination is a mechanism that takes place during gastrulation. This mechanism or cell movement happens mostly in the vegetal ...
is a constitutive process but its frequency is dramatically increased during periods of starvation. Invagination is a tubular process by which is formed the
autophagic Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
tube. Formation of the
autophagic Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
tubes is mediated through Atg7-dependent
ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
-like conjugation (Ublc) or via vacuolar transporter chaperone ( VTC) molecular complex which acts through
calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...
-dependent manner. Calmodulin involvement in tube formation is
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
independent process.


Vesicle formation

The mechanism of vesicle formation is based on lateral sorting mechanism. Changed composition of
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
molecules (
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
enrichment in the autophagic tubes due to removal of
transmembrane proteins A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
) leads spontaneous
vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
formation via phase separation mechanism. The process of microautophagic vesicle formation is similar to
multivesicular bodies Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can f ...
formation process


Vesicle expansion and scission

Enlargement of vesicle is mediated by binding
enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
inside of unclosed vesicle. Basically, this process is reversal to
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
. Process follows by pich of the vesicle into the lysosomal/vacuolar lumen. This process is independent on
SNARE SNARE proteins – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle fu ...
proteins.


Vesicle degradation and recycling

Vesicle moves freely in the lumen and during the time is degraded by
hydrolases Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...
(ec. Atg15p). Nutrients are then released by Atg22p.


Selective microautophagy

Process of non-selective microautophagy can be observed in all types of
eukaryotic cells Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
. On the other hand, selective microautophagy is commonly observed in
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
cells. Three types of selective microautophagy selective microautophagy can be distinguished: micropexophagy, piecemeal microautophagy of the nucleus and micromitophagy


References

{{reflist Cellular processes Programmed cell death