What is autophagy? Degradation, recycling, and a beneficial response to stress | Guido Kroemer
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Autophagy is a highly conserved adaptive response to stress during which a cell gathers unnecessary or damaged cellular components such as protein aggregates, pathogens, or organelles into vesicles and delivers them to lysosomes for destruction. In the process, proteins, lipids, carbohydrates, and nucleic acids are released and become available for energy and re-use. Autophagy's overarching goal is to maintain cellular homeostasis in the face of changing conditions and stress. In this clip, Dr. Guido Kroemer describes the spectacular biological phenomenon known as autophagy.
- Dr. Kroemer: So, autophagy is a spectacular phenomenon in cell biology, one that you can see with your eyes because cells become vacuolated when this process is induced. So you can see it by light microscopy and better, of course, by electron microscopy. It is a process that consists in sequestering portions of the cytoplasm of the cell and then digesting them to recycle the material and to degrade macromolecules into micromolecules, metabolites, and to allow rebuilding the structures that have been destroyed. So technically, it works in the sense that the mouth that is involved in this self-digestion process is the autophagosome. So, it will sequester portions of the cell in the cytoplasm. It can be entire organelles including mitochondria, it can be protein aggregates, it can be bacteria or viruses that invade the cell, and this autophagosome, once it closes, will fuse with the lysosomes, which is the sort of stomach of the cell. And in the lysosome, that has been fusing with the autophagosome, which is then called Autophagolysosome, the luminal content will then be digested.
- Rhonda: So you mentioned the digesting of these multiple organelles or mitochondria, but also protein aggregates, and viruses, bacteria, pieces of chromatin, and things all seem to be sort of things that at least in the sense, if you're looking at the aggregates, and you know, damage that occurs in a cell, seems to be something that's associated with aging in general. So it's sort of like, kind of seems like it's getting rid of all these damaging, potentially damaging, not just aging but also obviously, an infection. But this process is getting rid of these damaging, potentially damaging molecules and aggregates and mitochondria which are defective. What is the actual goal of autophagy is? Like you said, is to get rid of these defective things to then provide energy?
- Dr. Kroemer: Well, it's actually interesting to look at the history of autophagy. The name comes from "autos phagy" in Greek which means "self-eating." And it's actually a linguistic invitation to think about self-mutilation and self-destruction and cell death. And actually, the phenomenon is observed mostly in the context of stress. So cells, when they are stressed, will often undergo an autophagic reaction, which occurs before the cells die. And so, this chronology of the phenomenon has been also an invitation to think that autophagy is a mechanism that leads to cell death until it has been understood that inhibition of autophagy, which can only be achieved in a specific way by genetic tricks, will actually sensitize cells to cell death induction. And so, this means that autophagy is a means of adaptation to stress and a technique of the cell to avoid cell death. So, the primary goal of autophagy is adaptation to changing conditions and adaptation to external stress, and at the end, avoidance of the unwarranted demise of the cell.
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.
Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.
Overtime proteins unintentionally accumulate damage from reactive oxygen and nitrogen species. These compromised proteins aggregate together and can promote aging as well as progressive diseases such as Alzheimer's and Parkinson's disease.
Formed into or containing one or more vacuoles or small membrane-bound cavities within a cell.
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