Week1-3 – Physiological Roles of Autophagy
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Week1-3 – Physiological Roles of Autophagy

We have seen that autophagy is a mechanism
for self-digestion in our cells. Next, let’s discuss the usefulness of self-digestion
by autophagy to the cell. We currently know that autophagy has many
important roles in life, but here we’ll focus on three fundamental roles of autophagy. To explain the first of these, I’d like
to use the degradation of protein as one example, although autophagy degrades a wide range of molecules
within cells. In this slide we can see the daily flux of
amino acids and proteins in a human body. We ingest about 70 grams of protein from food
every day, which is digested into amino acids and delivered to cells throughout our bodies. However, this amount is far less than the
amount of proteins produced in our bodies; about 200 grams of proteins are made every
day from amino acids in our bodies. In addition, amino acids are also used for
other purposes, such as the synthesis of non-protein molecules, and a subset of amino acids is
excreted. This apparent shortfall in the flux of amino
acids and proteins can be explained by protein degradation. In fact, about 200 grams of proteins in our
bodies are degraded every day, and the resulting amino acids enter this flux. Autophagy is a major contributor to this degradation
process. This means that our cells degrade as much
protein as they synthesize. This may seem futile but actually has a very
important meaning. Continuous degradation and synthesis of cellular
components prevents the accumulation of “old” components, which can be harmful to cells
and accelerate the aging of cells and our bodies. In summary, autophagy plays an important role
in keeping cellular components fresh. The second example of the important roles
of autophagy is its function as a response to starvation. Here, we’ll consider protein degradation
as an example. Organisms, especially those living in nature,
often encounter starvation conditions. During these circumstances, the levels of
amino acids decrease, which results in the attenuation of protein synthesis. Cells need to urgently adapt to these conditions. Autophagy is strongly induced in
response to nutrient starvation, and degrades existing proteins to produce amino acids,
which are used for the synthesis of proteins required for adaptation to starvation, as
well as the production of energy and other important molecules. In addition to proteins, other cellular components
are also degraded and recycled by autophagy. Thus, autophagy plays an essential role for
cells to survive nutrient starvation. Next, let’s talk about the third example of
the fundamental roles of autophagy. Within cells, harmful materials often arise. For instance, some proteins that have denatured
and become abnormal due to stress or mutations can form aggregates, which are linked to neurodegeneration or liver disease. Dysfunctional mitochondria can produce
reactive oxygen species that can damage other parts of the cell, resulting in cellular aging
and neurodegeneration. Moreover, in mammals, some bacteria and viruses
invade cells and cause infectious diseases. Autophagy can eliminate large and harmful
materials, such as the examples we just thought about. Autophagy therefore plays an important role
in protecting us from cellular damage that results in aging and diseases. In addition to the three major roles we just
considered, recent studies have revealed that autophagy is implicated in many physiological
processes occurring within cells. Those shown here are a few of these processes. Evidence now indicates that autophagy is involved
in intracellular clearance, anti-aging processes, starvation responses, organelle homeostasis,
development and differentiation, and the presentation of antibodies. On the other hand, the failure of autophagy
is suggested to be linked to a number of human diseases, including neurodegeneration, liver disease, heart failure, diabetes, microviral infection and cancer. We’ll discuss this topic more in week 3.

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