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13 Autophagy: Reversing Cell Growth

Yoshinori Ohsumi


It is now well known that every cellular event requires a balance of synthesis and breakdown of many proteins. Every protein has its own lifetime within a wide range, from a few minutes to more than ten days. We do not yet know the determinants of the lifetime of each protein or the exact purpose of protein turnover, but a dynamic state of equilibrium must be crucial for the control of cell growth.

Proteins are not degraded spontaneously, but rather are degraded by active processes. There are two major pathways of intracellular protein degradation. First, the ubiqutin–proteasome system in the cytoplasm mediates the degradation of short-lived, damaged, or misfolded proteins (Hochstrasser 1996; Hershko and Ciechanover 1998). Proteins targeted for degradation are first tagged with a small protein, ubiquitin, and then digested by a huge proteinase complex, the proteasome. Both the ubiquitination and cleavage processes require ATP hydrolysis and are strictly dependent on recognition of target proteins by the sophisticated ubiquitin ligase system and the proteasome. Short-lived proteins play crucial roles in important cellular events such as transcriptional regulation and cell cycle control.

The second major pathway of intracellular protein degradation involves the degradation of long-lived proteins within a specific compartment, the lysosome/vacuole. So far, several delivery routes to this lytic compartment are proposed. The self-degradation of intracellular components in lysosomes is generally called autophagy, in contrast to heterophagy of extracellular materials (Mortimore and Poso 1987). Macroautophagy, the major autophagic pathway, begins with a so-called isolation membrane engulfing a portion...

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