View source for Chaperone-mediated autophagy

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Chaperone-mediated autophagy (CMA) is a lysosomal pathway leading to the breakdown of cytosolic proteins during times of prolonged starvation <ref>Dice J. Chaperone-Mediated Autophagy. Autophagy. 2007;3(4):295-299.</ref>. It is one of the more selective forms of [[Autophagy|autophagy]] due to its reliance on specific targeting motifs on its target proteins. This process is much more specific than other types of autophagy, like macroautophagy, which relies on randomly forming de novo double membrane [[Vesicle|vesicles]], called autophagosomes, arounds areas of cytoplasm and its associated proteins and organelles for degradation <ref>Mizushima N, Ohsumi Y, Yoshimori T. Autophagosome Formation in Mammalian Cells. Cell Structure and Function. 2002;27(6):421-429.</ref>. Also, in contrast to other forms of autophagy, the proteins to be degraded are not engulfed by[[Autophagosome|autophagosomes]] which fuse to [[Lysosome|lysosomes]], instead they are translocated across the lysosomal membrane in a receptor mediated process&nbsp;<ref>Lodish H. Molecular cell biology. New York: Freeman - MacMillan; 2016. 661-665</ref>. <br> 

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== Selectivity&nbsp;  ==

At the start of starvation, the normal response of the cell is to activate macroautophagy pathways to degrade random portions of the [[Cytosol|cytosol]]. However, if starvation occurs for more than 6-8 hours then a switch is made to the more selective CMA. As previously mentioned, a five residue long motif in the [[Polypeptide chain|polypeptide sequence]] is responsible CMA’s selectivity. The five residue motif is fairly specific in its requirements, however there is room for flexibility. The motif must contain a Glutamate (Q) at one end, one acidic residue (D or E), one basic residue (K or R), one hydrophobic residue (F, I, L or V) and one [[Amino acid residues|residue]] that can be either basic or hydrophobic (so long as it is not negative) <ref>Wang D, Peng Z, Ren G, Wang G. The different roles of selective autophagic protein degradation in mammalian cells. Oncotarget. 2015;6(35): 37098–37116</ref>. This targeting motif does not need to be in a position where it can be easily accessed on the protein, most proteins need partial unfolding for the motif to be reached <ref>Lodish H. Molecular cell biology. New York: Freeman - MacMillan; 2016. 661-665</ref>. While this motif is shared by all proteins that are degraded by CMA, the mere presence of this motif does not guarantee that the protein is a candidate for CMA <ref>Lodish H. Molecular cell biology. New York: Freeman - MacMillan; 2016. 661-665</ref>. The increased specificity of CMA allows the cell to preserve more vital components, to allow it to continue functioning for a long as possible, which would not be the case if macroautophagy were its only&nbsp;response, as this process may degrade essential components of the cell, hindering it.&nbsp;&nbsp; 

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