Figure 13–41 The role of the vacuole in controlling the size of plant cells. a plant cell can achieve a large increase in volume without increasing the volume of the cytosol. localized weakening of the cell wall orients a turgor-driven cell enlargement that accompanies the uptake of water into an expanding vacuole. The cytosol is eventually confined to a thin peripheral layer, which is connected to the nuclear region by strands of cytosol stabilized by bundles of actin filaments (not shown).
Figure 13–42 Four pathways to degradation in lysosomes. Materials in each pathway are derived from a different source. note that the autophagosome has a double membrane. In all cases, the final step is the fusion with lysosomes.
All cell types dispose of obsolete parts by a lysosome-dependent process called autophagy, or “self-eating.” The degradation process is important during normal cell growth and in development, where it helps restructure differentiating cells, but also in adaptive responses to stresses such as starvation and infection. Autophagy can remove large objects—macromolecules, large protein aggregates, and even whole organelles—that other disposal mechanisms such as proteasomal degradation cannot handle. Defects in autophagy may prevent cells from clearing away invading microbes, unwanted protein aggregates and abnormal proteins, and thereby contribute to diseases ranging from infectious disorders to neurodegeneration and cancer.
In the initial stages of autophagy, cytoplasmic cargo becomes surrounded by a double membrane that assembles by the fusion of small vesicles of unknown origin, forming an autophagosome (Figure 13–43). A few tens of different proteins have been identified in yeast and animal cells that participate in the process, which must be tightly regulated: either too little or too much can be deleterious. The whole process occurs in the following sequence of steps: 1.
Induction by activation of signaling molecules: Protein kinases (including the mTOR complex 1, discussed in Chapter 15) that relay information about the metabolic status of the cell, become activated and signal to the autophagic machinery.
2.
Nucleation and extension of a delimiting membrane into a crescent-shaped cup: Membrane vesicles, characterized by the presence of ATG9, the only transmembrane protein involved in the process, are recruited to an assembly site, where they nucleate autophagosome formation. ATG9 is not incorporated into the autophagosome: a retrieval pathway must remove it from the assembling structure.
3.
Closure of the membrane cup around the target to form a sealed double-membrane-enclosed autophagosome.
4.
Fusion of the autophagosome with lysosomes, catalyzed by SNAREs.
5.
Digestion of the inner membrane and the lumenal contents of the autophagosome.
Autophagy can be either nonselective or selective. In nonselective autophagy, a bulk portion of cytoplasm is sequestered in autophagosomes. It might occur, for example, in starvation conditions: when external nutrients are limiting, metabolites derived from the digestion of the captured cytosol might help the cell survive. In selective autophagy specific cargo is packaged into autophagosomes that tend to contain little cytosol, and their shape reflects the shape of the cargo. Selective autophagy mediates the degradation of worn out, or otherwise unwanted, mitochondria, peroxisomes, ribosomes, and ER; it can also be used to destroy invading microbes.
Figure 13–43 A model of autophagy.