|
Summary of Research Projects (Supports in 2004
Fiscal Year)
| Subjects |
Role of Autophagy in the Heart. |
| Representative researcher |
The Tokyo Metropolitan Institute of Medical Science
Noboru MIZUSHIMA |
| Autophagy is an intracellular,
bulk degradation process, through which a portion of cytoplasm
is delivered to lysosomes to be degraded. Although the role
of autophagy has been well studied in yeast cells, its physiological
role in higher eukaryotes is still obscure. We therefore analyzed
organ-specific roles of autophagy, particularly focusing on
the heart and the nervous system. Although the activity of
autophagy is very high in the heart, the abnormality of the
heart muscles themselves was minimal even in the absence of
autophagy under physiological conditions. Heart autophagy might
be important under some stress conditions. In contrast, loss
of autophagy in the brain causes neurodegeneration. Neural
cell-specific Atg5 deficient mice develop progressive deficits
in motor function that are accompanied by the accumulation
of cytoplasmic inclusion bodies in neurons. In Atg5-/- neurons,
diffuse intracellular abnormal proteins first accumulate, followed
by generation of aggregates and inclusions. These results suggest
that continuous clearance of diffuse cytosolic proteins by
autophagy is important for preventing the accumulation of abnormal
proteins, particularly in neurons but less important in the
heart muscles. Therefore the importance of autophagy differs
among tissues. |
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