[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 an 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, it 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.