Mini ReviewThree faces of mortalin: A housekeeper, guardian and killer
Section snippets
The discovery of twin mortalins
Mortalin has come a long way since it was first cloned and identified to be associated with cellular mortality by virtue of its presence in the cytosolic fractions of serially passaged mouse embryonic fibroblasts (MEF), and of mortal hybrids obtained by the fusion of mortal (MEF) and immortal (MN48-1, derivative of NIH 3T3) cells. Immortal cells seemed to lack this protein in their cytosolic fractions. cDNA cloning and homology search placed it in the heat shock protein 70 (hsp70) family (
Mortalin in its housekeeping mode
Mortalin is the major mitochondrial protein (Bhattacharyya et al., 1995) and it plays a central role in the elaborate translocation system for efficient import and export of proteins (Koehler, 2004, Rehling et al., 2004, Wiedemann et al., 2004). Its role in cell viability and mitochondrial biogenesis was underscored by experimental data including (i) the yeast cells knocked out for mortalin homologue (Sscl) were lethal (Craig et al., 1987) and (ii) the loss of function mutations of mthsp70
Mortalin in its guardian mode
The biological impact of mortalin function is not restricted to its mitochondrial locale. Subcellular fractionation and immunofluorescence microscopy have revealed that mortalin is not only present in mitochondria but also in other extra-mitochondrial sites (Ran et al., 2000, Poindexter et al., 2002). In parallel, its multiple binding partners have revealed its diverse functional skills (Fig. 2). Although mortalin did not consent with other members of heat shock protein 70 family due to its
In cancers
Tumors are known to lead more “stressful” lives compared to the normal cells. This is particularly the case considering that its immortal state carries added demands for continuous rapid proliferation; competition for basic cellular needs (space, nutrient and oxygen); hostility of new cellular environments, particularly for “adventurous” metastases; and most significantly, the accumulation of mutated proteins as a result of genomic instability. Just as senescence is considered, at least in the
Perspectives: mortalin-based interventions
Bearing in mind the three egos of mortalin i.e., as an essential housekeeping gene, as a guardian chaperone that is activated during stress and cause killing of the old, it may seem rather audacious to therapeutically control this chaperone’s temperaments. Some hints, however, at fine-tuning these mortalin paradoxes for achieving healthy aging and to forward novel approaches in treating of aging-associated diseases, such as cancer, can be glimpsed from several key basic studies over the past
Acknowledgement
Authors thank Zeenia Kaul for the artwork.
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