Mortalin is a member of Hsp70 family of stress chaperones. It was first identified as a protein involved in the senescence of
mouse cells. Genetic studies revealed that there are two mouse mortalin alleles coding for two proteins (mot-1 and mot-2) that differ in
only two amino acids in the carboxy-terminus, but have contrasting activities. Whereas mot-1 accelerated senescence, mot-2 extended the
lifespan of mouse cells in culture. In human cells, only one kind of mortalin protein has been identified so far and is shown to be functionally
equivalent to mouse mot-2. Whereas mortalin is enriched in cancer cells and contributes to carcinogenesis, the old age brain disorders
show its deficiency. As we demystify its deux de machina, accumulating evidence reveal that mortalin may be “druggable” bidirectionally
to either treat cancer or neuro-degenerative disorders.
Keywords: Mortalin, chaperone, cancer, aging, target, therapy, Hsp70, alleles, senescence, neuro-degenerative disorders.
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