Autophagosomes

Autophagosomes play many important roles in the human body and are critical responses to a number of factors. Autophagosomes are cellular vesicles that ingest cellular debris, such as fragments of membranes, whole organelles, and proteins, and transport the debris to lysosomes. The autophagosomes then fuse with lysosomes and protease from the lysosome digest the transported cellular components. Some of the roles that autophagosomes play in the human body include involvement in a response to starvation, programmed cell death (apoptosis), and they can also be induced in patients with degenerative diseases.

Autophagy

Autophagy

The actual process of delivering cellular debris to lysosomes is known as autophagy, and there are three different proposed types of autophagy: macroautophagy, microautophagy, and chaperon-mediate autophagy. Macroautophagy is believed to be major process for protein degradation, and in this process, cytoplasmic components are enclosed by an isolation membrane, a membrane like sac. This isolation membrane becomes an autophagosome when the isolation membrane transforms into a double membrane. Autophagosomes mature by fusing with endosomes to form amphisomes or intermediate autophagic vacuoles. These matured autophagosomes then undergo the final fusion with lysosomes.

Although the general theory of autophagy and the formation of autophagosomes are understood, the detailed molecular mechanism is not well known. However, scientists do know that autophagosomes form from autophagosome precursors, which are small membrane structures that elongate. Class III PtdIns 3-kinase is a requirement in an early step of the autophagic pathway. PtdIns 3-kinase is a protein kinase that is involved in the cellular trafficking of proteins and vesicles in the human body. Researchers believe the Apg proteins are also involved in the elongation of the isolation membrane to form autophagosomes, and it is known that the ubiquitin like conjugation system, Apg12, is required for autophagosome formation.

Scientists also know that another ubiquitin like system, the LC3 system, is involved in autophagy, because the LC3 system was the first protein identified on the autophagosome membrane. The LC3 system is similar to the Apg12 system involved in autophagy, Apg12Apg5Apg16, but there is one key difference. When an autophagosome is formed from the isolation membrane, the Apg12Apg5
Apg16
protein comes off of the membrane, but the LC3 protein system stays on the membrane. However, researchers do not believe the LC3 system to be important in the lysosome- autophagosome fusion process. Microtubules are the important component necessary for autophagosomes to fuse with lysosomes.

While the study of the molecular mechanism of autophagosome formation and its characteristics may not seem important to the casual observer, this research is indeed quite important because of autophagosomes’ involvement in a number of human diseases. If scientists can determine what truly triggers autophagosomes, they may be able to stimulate the formation of autophagosomes in patients that do not have enough apoptosis, which is one of the major problems for cancer patients. Or vice versa, if a patient has too many healthy cells that are dying and viable cellular components that are being transported and degraded by autophagosomes and lysosomes, respectively, then researchers and physicians might be able to shut off the autophagy process.

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